scholarly journals Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Vasily V. Sinyov ◽  
Anastasia I. Ryzhkova ◽  
Elena V. Galitsyna ◽  
Zukhra B. Khasanova ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Carotid Atherosclerosis ◽  
Nuclear Dna ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Atherosclerotic Lesions ◽  
Dna Mutations ◽  
Blood Leukocyte ◽  
Study Participants

Mutations of mtDNA, due to their higher frequency of occurrence compared to nuclear DNA mutations, are the most promising biomarkers for assessing predisposition of the occurrence and development of atherogenesis. The aim of the present article was an analysis of correlation of several mitochondrial genome mutations with carotid atherosclerosis. Leukocytes from blood of study participants from Moscow polyclinics were used as research material. The sample size was 700 people. The sample members were diagnosed with “atherosclerosis” on the basis of ultrasonographic examination and biochemical and molecular cell tests. DNA was isolated from blood leukocyte samples of the study participants. PCR fragments of DNA, containing the region of 11 investigated mutations, were pyrosequenced. The heteroplasmy level of these mutations was detected. Statistical analysis of the obtained results was performed using the software package SPSS 22.0. According to the obtained results, an association of mutations m.652delG, m.3336C>T, m.12315G>A, m.14459G>A m.15059G>A with carotid atherosclerosis was found. These mutations can be biomarkers for assessing predisposition to this disease. Additionally, two single nucleotide substitutions (m.13513G>A and m.14846G>A), negatively correlating with atherosclerotic lesions, were detected. These mutations may be potential candidates for gene therapy of atherosclerosis and its risk factors.

A new marker of human aging: heteroplasmy level of mitochondrial genome mutations

2021 ◽  
pp. 4-9
Author(s):  
В.В. Синёв ◽  
А.И. Рыжкова ◽  
М.Д. Сазонова ◽  
Н.А. Дорощук ◽  
Т.В. Кириченко ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Medical Science ◽  
Biological Aging ◽  
Human Aging ◽  
Nucleotide Substitutions ◽  
Blood Leukocytes ◽  
Single Nucleotide ◽  
Cellular Models ◽  
Mtdna Mutations ◽  
Study Participants

Введение. Геронтология - это наука о причинах биологического старения организма. Ее составной частью является гериатрия - наука о болезнях и факторах, вызывающих старение. Полагаем, что митохондриальные мутации, затрагивающие гены белковых субъединиц дыхательной цепи, а также транспортных и рибосомальных РНК, могут являться одним из факторов старения индивидов. При этом, согласно данным литературы, проблема связи мутаций митохондриального генома со старением индивидов изучена недостаточно. Цель исследования - анализ ассоциации уровня гетероплазмии мутаций мтДНК с возрастом индивидов. Методика. Объектом исследования была выборка жителей Московского региона состоящая из 712 участников. ДНК выделяли из образцов лейкоцитов крови участников исследования с помощью метода фенол-хлороформной экстракции. Была проведена ПЦР фрагментов ДНК, содержащих область исследованных мутаций. Полученные амплификаты были пиросеквенированы. Анализ уровня гетероплазмии данных мутаций был проведен с помощью количественного метода, разработанного авторами статьи. Для подсчета уровня гетероплазмии мутаций по данным пирограммы использовалась ранее разработанная авторами формула. Результаты. Показано, что с возрастом индивидов положительно коррелируют однонуклеотидные замены митохондриального генома m.12315G>A, m.14459G>A и m.15059G>A (p≤0,05) и отрицательно - m.1555A>G и m.14846G>A (p≤0,05). Мутации m.652insG и m.13513G>A отрицательно коррелируют с возрастом на уровне значимости p≤0,1. Заключение. Обнаружены 3 однонуклеотидные замены m.14459G>A, m.15059G>A и m.12315G>A генов MT-ND6, MT-CYTB и MT-TL2 (соответственно) ассоциированные со старением организма человека. Данные мутации могут быть использованы для создания молекулярно-клеточных моделей старения. В то же время, выявлены мутации m.1555A>G, m.652insG (ген MT-RNR1), m.14846G>A (ген CYTB) и m.13513G>A (ген MT-ND5), отрицательно коррелирующие с возрастом индивидов. Данные мутации могут быть использованы при генотерапии для замедления старения людей. Introduction. Gerontology is a branch of science that focuses on the causes of biological aging. Its clinical component is geriatrics, a branch of medical science that focuses on diseases and factors causing aging. We hypothesize that mitochondrial mutations that affect genes of protein subunits of the respiratory chain, and, also, transport and ribosomal RNAs may be factors of aging. Meanwhile, according to the literature, the connection of mitochondrial genome mutations with aging has not been adequately studied. Aim. To analyze the association of heteroplasmy level in mtDNA mutations with the age of individuals. Methods. A sample of inhabitants of the Moscow region, composed of 712 study participants, was enrolled in the study. DNA was isolated from blood leukocytes by phenol chloroform extraction, and PCR of DNA fragments, containing the region of the studied mutations was performed. The obtained amplificates were pyrosequenced. These mutations were analyzed for the heteroplasmy level using a quantitative method developed by the authors. To determine the heteroplasmy level of mutations from the pyrogram data, a formula was used that had earlier been developed by the authors. The results were statistically analyzed with the software package, IBM SPSS Statistics, version 27.0 (SPSS Inc., USA). Results. Analysis of mutations showed that single nucleotide substitutions of the mitochondrial genomes m.12315G>A, m.14459G>A and m.15059G>A correlated positively with subject age (p≤0.05) whereas m.1555A>G and m.14846G>A correlated negatively (p≤0.05). Mutations m.652insG and m.13513G>A tended to correlate negatively with aging (p≤0.1). Conclusion. Three single nucleotide substitutions were found: m.14459G>A, m.15059G>A, and m.12315G>A of genes MT-ND6, MT-CYTB, and MT-TL2, respectively, that are associated with human aging. Thus, these mutations may be used for creating molecular cellular models of aging. At the same time, mutations m.1555A>G, m.652insG (gene MT-RNR1), m.14846G>A (gene CYTB), and m.13513G>A (gene MT-ND5) were detected, which correlate with aging negatively. These mutations may be used in gene therapy to slow aging.

scholarly journals mtDNA polymorphism and metabolic inhibition affect sperm performance in conplastic mice

Reproduction ◽  
2017 ◽  
Vol 154 (4) ◽  
pp. 341-354 ◽  
Author(s):  
Maximiliano Tourmente ◽  
Misa Hirose ◽  
Saleh Ibrahim ◽  
Damian K Dowling ◽  
Daniel M Tompkins ◽  
...  
Keyword(s):  
Nuclear Dna ◽  
Reproductive Traits ◽  
Inbred Strains ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
Atp Production ◽  
Dna Mutations ◽  
Performance Response ◽  
Nuclear Background ◽  
Male Specific

Whereas a broad link exists between nucleotide substitutions in the mitochondrial genome (mtDNA) and a range of metabolic pathologies, exploration of the effect of specific mtDNA genotypes is on-going. Mitochondrial DNA mutations are of particular relevance for reproductive traits, since they are expected to have profound effects on male specific processes as a result of the strict maternal inheritance of mtDNA. Sperm motility is crucially dependent on ATP in most systems studied. However, the importance of mitochondrial function in the production of the ATP necessary for sperm function remains uncertain. In this study, we test the effect of mtDNA polymorphisms upon mouse sperm performance and bioenergetics by using five conplastic inbred strains that share the same nuclear background while differing in their mitochondrial genomes. We found that, while genetic polymorphisms across distinct mtDNA haplotypes are associated with modification in sperm progressive velocity, this effect is not related to ATP production. Furthermore, there is no association between the number of mtDNA polymorphisms and either (a) the magnitude of sperm performance decrease, or (b) performance response to specific inhibition of the main sperm metabolic pathways. The observed variability between strains may be explained in terms of additive effects of single nucleotide substitutions on mtDNA coding sequences, which have been stabilized through genetic drift in the different laboratory strains. Alternatively, the decreased sperm performance might have arisen from the disruption of the nuclear DNA/mtDNA interactions that have coevolved during the radiation ofMus musculussubspecies.

scholarly journals The Role of Mitochondria in Carcinogenesis

2021 ◽  
Vol 22 (10) ◽  
pp. 5100
Author(s):  
Paulina Kozakiewicz ◽  
Ludmiła Grzybowska-Szatkowska ◽  
Marzanna Ciesielka ◽  
Jolanta Rzymowska
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Dna Polymorphisms ◽  
Gene Encoding ◽  
Dna Mutations ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Gene Coi ◽  
The Impact

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

scholarly journals The Role of the Mitochondrial Genome in Ageing and Carcinogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Anna M. Czarnecka ◽  
Ewa Bartnik
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Genome ◽  
Cancer Cells ◽  
Successful Aging ◽  
Mitochondrial Haplogroups ◽  
Mitochondrial Dna Mutations ◽  
Dna Mutations

Mitochondrial DNA mutations and polymorphisms have been the focus of intensive investigations for well over a decade in an attempt to understand how they affect fundamental processes such as cancer and aging. Initial interest in mutations occurring in mitochondrial DNA of cancer cells diminished when most were found to be the same mutations which occurred during the evolution of human mitochondrial haplogroups. However, increasingly correlations are being found between various mitochondrial haplogroups and susceptibility to cancer or diseases in some cases and successful aging in others.

scholarly journals Response to: Comment on “Role of Mitochondrial Genome Mutations in Pathogenesis of Carotid Atherosclerosis”

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Igor A. Sobenin ◽  
Margarita A. Sazonova ◽  
Vasily V. Sinyov ◽  
Anastasia I. Ryzhkova ◽  
Elena V. Galitsyna ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Carotid Atherosclerosis

scholarly journals Using the ITS2 transcribed spacer of nuclear ribosomal DNA to identify species of the genus Nitraria

2020 ◽  
Vol 24 ◽  
pp. 00009
Author(s):  
Evgeny V. Banaev ◽  
Tatiana A. Poliakova ◽  
Mariya A. Tomoshevich ◽  
Taigana Ak-Lama
Keyword(s):  
Ribosomal Dna ◽  
Dna Sequences ◽  
Nuclear Ribosomal Dna ◽  
Its2 Region ◽  
Nucleotide Substitutions ◽  
Single Nucleotide ◽  
High Importance ◽  
Single Nucleotide Deletion ◽  
Nucleotide Variability

Intragenomic polymorphism of ITS2 of nuclear ribosomal DNA sequences was analysed in 30 samples belonging to Nitraria schoberi, N. sibirica. The nucleotide variability of the ITS2 region was detected in the studied Nitraria species as single-nucleotide substitutions (mainly transitions) and single-nucleotide deletion. Five ribotypes of Nitraria were identified in Russia, Kazakhstan and Tajikistan. These ribotypes formed two haplogroups that belong to the species N. schoberi and N. sibirica, respectively. The high importance of the discriminatory role of the ITS2 spacer in identifying species of the genus Nitraria is confirmed.

Mitochondrial DNA mutations in patients with myelodysplastic syndromes

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3118-3125 ◽  
Author(s):  
Myung Geun Shin ◽  
Sachiko Kajigaya ◽  
Barbara C. Levin ◽  
Neal S. Young
Keyword(s):  
Amino Acid ◽  
Mitochondrial Genome ◽  
Direct Sequencing ◽  
Bone Marrow Failure ◽  
Healthy Controls ◽  
Nucleotide Substitutions ◽  
Bone Marrow Failure Syndrome ◽  
Hematopoietic Stem ◽  
Dna Mutations ◽  
New Mutations

Abstract We undertook to systematically analyze the entire mitochondrial genome by gene amplification and direct sequencing in 10 patients with myelodysplasia; results were compared with concomitantly studied 8 healthy volunteers as well as mtDNA sequences in a standard database. Nucleotide changes that were present in our healthy controls as well as those in published databases were counted as polymorphisms. Overall, there was no increase in the number of mtDNA genes harboring polymorphisms or “new” mutations between our patients and healthy controls, although there were a few more mtDNA changes resulting in amino acid changes in myelodysplasia (9 in 8 controls versus 16 in 10 patients). Thirty new mutations, all nucleotide substitutions, were found among the 10 patients, distributed throughout the mitochondrial genome; 5 mutations resulted in amino acid changes. None of the mutations in controls produced amino acid changes. We were not able to confirm previously described mutations in sideroblastic anemia or “hot spots” in the cytochrome c oxidase I and II genes. Our data do not support a major role for mitochondrial genomic instability in myelodysplasia, and they fail to reproduce previous reports of significant or widespread mitochondrial mutations in this disease. Modest changes in mutation numbers and mitochondrial microsatellites may be evidence of increased mutagenesis in mtDNA, or, more likely, a reflection of limited clonality among hematopoietic stem cells in this bone marrow failure syndrome.

scholarly journals Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk

2021 ◽  
Vol 22 (9) ◽  
pp. 4459
Author(s):  
Siarhei A. Dabravolski ◽  
Evgeny E. Bezsonov ◽  
Mirza S. Baig ◽  
Tatyana V. Popkova ◽  
Ludmila V. Nedosugova ◽  
...  
Keyword(s):  
Liver Disease ◽  
Causative Role ◽  
Nucleotide Polymorphisms ◽  
Mitochondrial Mutations ◽  
Single Nucleotide ◽  
Alcoholic Fatty Liver ◽  
Dna Mutations ◽  
Life Threatening ◽  
Mitochondria Dna

NAFLD (non-alcoholic fatty liver disease) is a widespread liver disease that is often linked with other life-threatening ailments (metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, atherosclerosis, obesity, and others) and canprogress to more severe forms, such as NASH (non-alcoholic steatohepatitis), cirrhosis, and HCC (hepatocellular carcinoma). In this review, we summarized and analyzed data about single nucleotide polymorphism sites, identified in genes related to NAFLD development and progression. Additionally, the causative role of mitochondrial mutations and mitophagy malfunctions in NAFLD is discussed. The role of mitochondria-related metabolites of the urea cycle as a new non-invasive NAFLD biomarker is discussed. While mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) canbe used as effective diagnostic markers and target for treatments, age and ethnic specificity should be taken into account.

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