Mitochondrial DNA haplotypes from the displacement-loop (D-loop) region (436 bp) were genotyped and sequenced in Japanese Black beef cattle raised in the same herd. Correlation coefficients between mitochondrial DNA haplotypes, maternal lineage, birth weight, preweaning average daily gain, weaning weight, post weaning average daily gain and yearling weight were computed. The objective was to study the relationship between maternal and postnatal growth traits and to investigate if postnatal growth of calves to yearling age could be accurately predicted from mitochondrial DNA haplotypes. Results of the phylogenetic analysis revealed 17 maternal lineages and four mitochondrial DNA haplotypes. There were strong, positive and highly significant (p,0.001) correlations among maternal traits ranging from 0.52 to 0.98. Similarly, among postnatal growth traits, most of the correlations were also strong, positive and highly significant (p,0.001); the highest correlation of 0.94 was between preweaning ...
The genetic diversity of Setipinna taty, which is commercially fished in the China Sea, was studied based on mitochondrial DNA control region sequences. PCR was used to amplify the control region fragment in 100 individuals of S. taty collected from Weihai (WH), Yantai (YT), Zhoushan (ZS), Xiangshan (XS), and Ninghai (NH) in China. A control region fragment of 656 bp was successfully sequenced in these 100 individuals. The A+T content of this S. taty control region was 71.7%; 172 variable sites and 62 haplotypes were found.
Although rapid changes in copy number and gene order are common within plant mitochondrial genomes, associated patterns of gene transcription are underinvestigated. Previous studies have shown that the gynodioecious plant species Silene vulgaris exhibits high mitochondrial diversity and occasional paternal inheritance of mitochondrial markers. Here we address whether variation in DNA molecular markers is correlated with variation in transcription of mitochondrial genes in S. vulgaris collected from natural populations. We analyzed RFLP variation in two mitochondrial genes, cox1 and atp1, in offspring of ten plants from a natural population of S. vulgaris in Central Europe. We also investigated transcription profiles of the atp1 and cox1 genes. Most DNA haplotypes and transcription profiles were maternally inherited; for these, transcription profiles were associated with specific mitochondrial DNA haplotypes. One individual exhibited a pattern consistent with paternal inheritance of mitochondrial DNA;
Objective Using real-time fluorescence quantitative PCR to detect mitochondrial DNA content changes within HepG2 cells induced by d4T and AZT. Methods HepG2 cells were treated with different concentrations(0,3,10,100,200,300μmol/L) of d4T and AZT respectively for two weeks. And then mitochondrial DNA contents were detected by real-time fluorescence quantitative PCR. Results Real-time fluorescence quantitative PCR was set up successfully to detect mitochondrial DNA contents. Mitochondrial DNA relative amounts were 96.94±5.77, 53.73±7.14, 20.78±3.10, 1.37±0.29 respectively with d4T concentrations of 0, 3, 10, 100μmol/L. The differences between groups were significant(P0.01). However, they were 96.94±5.77, 108.84±7.80, 172.56±4.70, 199.51±10.37, 158.74±6.64 and 64.06±6.27 respectively with AZT concentrations of 0, 3, 10, 100, 200, 300μmol/L, and the differences between groups were significant(P0.01). Conclusions It is practicable to detect mitochondrial DNA contents with real-time fluorescence
Exciting new studies are increasingly strengthening the link between mitochondrial mutagenesis and tumor progression. Here we provide a comprehensive review and meta-analysis of studies reporting on mitochondrial DNA mutations in common human cancers. We discuss possible mechanisms by which mitochondrial DNA mutations may influence carcinogenesis, outline important caveats for interpreting the detected mutations--particularly differentiating causality from association--and suggest how new mutational assays may help resolve fundamental controversies in the field and delineate the origin and expansion of neoplastic cell lineages. Finally, we discuss the potential clinical utility of mtDNA mutations for improving the sensitivity of early cancer diagnosis, rapidly detecting cancer recurrence, and predicting the disease outcome.. ...
From previous studies, it is known that the low OA risk haplogroup J is associated with lower serum levels of markers of collagen type-II degradation and of matrix metalloproteinases, but all of these studies failed to address the key question arising from this large body of evidence: What is the functional role of these mtDNA haplogroups?. To answer this question, Fernandez-Moreno et al7 used cytoplasmic hybrid (cybrid) cell lines. Cybrids incorporate mitochondria from human subjects and perpetuate the mtDNA-encoded components while maintaining the nuclear background of different cybrid lines as constant.16 Thus, this technique allows investigators to assess the influence of mtDNA variation on cell function. To investigate the role of mtDNA haplogroups, they also created cybrids using osteosarcoma cell lines with the same nuclear background, one of them harbouring the haplogroup J (which protects against OA) and another harbouring the haplogroup H (linked to higher risk of OA).. The cybrids ...
|jats:p|Mitochondrial DNA (mtDNA) is almost entirely maternally inherited. Thousands of copies of mtDNA are present in every nucleated cell and in most normal individuals these are virtually identical (homoplasmy). mtDNA diseases may be caused by mutations in either mitochondrial or nuclear genes and, hence, give rise to maternal or autosomal patterns of inheritance. Antenatal diagnosis of mitochondrial diseases based on chorionic villous sampling is available for Mendelian disorders and the syndromes caused by mutations at bp 8993 (associated with Leighs syndrome and neurogenic weakness, ataxia and retinitis pigmentosa (NARP)). However, prenatal diagnosis of many other maternally inherited mtDNA diseases is less reliable because it is not possible to predict with confidence the way in which heteroplasmic mtDNA mutations segregate within tissues and find clinical expression. This review focuses on the substantial progress in genetics that has been made recently, and on the management options that
Saeidi, Z., Rezvani Gilkolaei, S., Soltani, M. (2017). Short communication: Population genetic structure studies of Liza aurata based on mtDNA control region sequences analyses in the southern coasts of the Caspian Sea, Iranian Journal of Fisheries Sciences, 17(4), pp. 1341-1348. doi: 10.22092/ijfs. ...
Mitochondrial DNA (mtDNA) copy number regulation is altered in several human mtDNA-mutation diseases and it is also important in a variety of normal physiological processes. Mitochondrial transcription factor A (TFAM) is essential for human mtDNA transcription and we demonstrate here that it is also a key regulator of mtDNA copy number. We initially performed in vitro transcription studies and determined that the human TFAM protein is a poor activator of mouse mtDNA transcription, despite its high capacity for unspecific DNA binding. Next, we generated P1 artificial chromosome (PAC) transgenic mice ubiquitously expressing human TFAM. The introduced human TFAM gene was regulated in a similar fashion as the endogenous mouse Tfam gene and expression of the human TFAM protein in the mouse did not result in down-regulation of the endogenous expression. The PAC-TFAM mice thus had a net overexpression of TFAM protein and this resulted in a general increase of mtDNA copy number. We used a
Mitochondrial DNA (mtDNA) heteroplasmy is a potential genetic marker for forensic mtDNA analysis as well as phylogenic studies. Frequency of mtDNA …
TY - JOUR. T1 - Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. AU - Kang, Eunju. AU - Wu, Jun. AU - Gutierrez, Nuria Marti. AU - Koski, Amy. AU - Tippner-Hedges, Rebecca. AU - Agaronyan, Karen. AU - Platero-Luengo, Aida. AU - Martinez-Redondo, Paloma. AU - Ma, Hong. AU - Lee, Yeonmi. AU - Hayama, Tomonari. AU - Van Dyken, Crystal. AU - Wang, Xinjian. AU - Luo, Shiyu. AU - Ahmed, Riffat. AU - Li, Ying. AU - Ji, Dongmei. AU - Kayali, Refik. AU - Cinnioglu, Cengiz. AU - Olson, Susan. AU - Jensen, Jeffrey. AU - Battaglia, David. AU - Lee, David. AU - Wu, Diana. AU - Huang, Taosheng. AU - Wolf, Don P.. AU - Temiakov, Dmitry. AU - Belmonte, Juan Carlos Izpisua. AU - Amato, Paula. AU - Mitalipov, Shoukhrat. PY - 2016/12/8. Y1 - 2016/12/8. N2 - Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type ...
Genetic Relationships of Cattle Breeds Assessed by PCR-RFLP of the Bovine Mitochondrial DNA D-loop Region - Bos Taurus;Bos Indicus;Mitochondrial DNA;PCR-RFLP;Genetic Distance;
The present invention provides methods for rapid forensic analysis of mitochondrial DNA and methods for characterizing heteroplasmy of mitochondrial DNA, which can be used to assess the progression of mitochondrial diseases.
Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.
BackgroundThe mitochondrial DNA depletion syndrome is an autosomal recessive disorder of infancy or childhood characterized by decreased mitochondrial DNA copy
PubMed journal article: Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Download Prime PubMed App to iPhone, iPad, or Android
Recombinant DNA techniques have been used to quantitate the amount of nucleotide sequence divergence in the mitochondrial DNA population of individual normal humans. Mitochondrial DNA was isolated from the peripheral blood lymphocytes of five normal humans and cloned in M13 mp11; 49 kilobases of nucleotide sequence information was obtained from 248 independently isolated clones from the five normal donors. Both between- and within-individual differences were identified. Between-individual differences were identified in approximately 1/200 nucleotides. In contrast, only one within-individual difference was identified in 49 kilobases of nucleotide sequence information. This high degree of mitochondrial nucleotide sequence homogeneity in human somatic cells is in marked contrast to the rapid evolutionary divergence of human mitochondrial DNA and suggests the existence of mechanisms for the concerted preservation of mammalian mitochondrial DNA sequences in single organisms.. ...
Many nucleoside analogue antiretroviral drugs (NRTIs) impair mitochondrial DNA (mtDNA) replication leading to reversible mtDNA depletion. It is unknown whether these drugs additionally cause mtDNA mutation. We recruited 35 HIV infected persons aged 50 years and under. Subjects were stratified by lifetime NRTI exposure. Skeletal muscle biopsies were subjected to COX (cytochrome-c oxidase) histochemistry, and individual fibres were laser captured for molecular analyses. Untreated patients showed negligible COX defects (mean 0.1%, SD 0.1%). Heavily NRTI-treated patients showed high level COX defects (mean 3.0%, SD 3.4%, maximum 9.8%). Difference between groups was statistically significant (p=0.002). Molecular analysis of individual COX-deficient fibres from treated subjects showed that the majority contained high proportional levels of mtDNA large-scale deletion mutations (41/70 fibres, 59%). Deleted species comprised a variety of mutations, each clonal within an individual fibre. No deleted mtDNA ...
Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C | T and A | G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational
TY - JOUR. T1 - Aberrant nucleo-cytoplasmic cross-talk results in donor cell mtDNA persistence in cloned embryos. AU - Lloyd, Rhiannon. AU - Lee, J.. AU - Alberio, R.. AU - Bowles, E.. AU - Ramalho-Santos, J.. AU - Campbell, K.. AU - St John, J.. PY - 2006/4. Y1 - 2006/4. N2 - Mitochondrial DNA is an extranuclear genome normally maternally inherited through the oocyte. However, the use of nuclear transfer can result in both donor cell and recipient oocyte mitochondrial DNA persisting through to blastocyst and being transmitted to the offspring. The degree of donor mitochondrial DNA transmission appears to be random and currently no evidence exists to explain this phenomenon. To determine whether this is a dilution factor or directly related to the transcriptional status of the donor cell in respect of mitochondrial DNA transcription factors, we have generated sheep nuclear transfer embryos using donor cells: (1) possessing their full mitochondrial DNA complement, (2) those partially depleted, ...
Mitochondrial DNA (mtDNA or mDNA) is the DNA located in mitochondria, cellular organelles within eukaryotic cells that convert chemical energy from food into a form that cells can use, adenosine triphosphate (ATP). Mitochondrial DNA is only a small portion of the DNA in a eukaryotic cell; most of the DNA can be found in the cell nucleus and, in plants and algae, also in plastids such as chloroplasts. In humans, the 16,569 base pairs of mitochondrial DNA encode for only 37 genes. Human mitochondrial DNA was the first significant part of the human genome to be sequenced. In most species, including humans, mtDNA is inherited solely from the mother. Since animal mtDNA evolves faster than nuclear genetic markers, it represents a mainstay of phylogenetics and evolutionary biology. It also permits an examination of the relatedness of populations, and so has become important in anthropology and biogeography. Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA ...
Mitochondrial dysfunction, generally characterized as a loss of efficiency in oxidative phosphorylation, is a hallmark of aging and a variety of chronic diseases. Mitochondrial dysfunction results in inefficient cellular energy production and in increased levels of reactive oxygen species (ROS) which may damage lipids, proteins, and nucleic acids. Mitochondrial dysfunction also affects the expression of nuclear genes involved in metabolism, growth, differentiation, and apoptosis. All these changes may explain the contribution of mitochondrial dysfunction to chronic and complex human diseases. A major limitation to the routine evaluation of mitochondrial dysfunction in clinical practice is the lack of reliable measures of mitochondrial dysfunction available for clinical use. Mitochondrial DNA copy number (mtDNA-CN) is a promising biomarker of mitochondrial dysfunction that has the potential to become widely available in clinical practice. Other measures of mitochondrial dysfunction, including ...
Although highly active antiretroviral therapy (HAART) has been extremely effective in lowering AIDS incidence among patients infected with HIV, certain drugs included in HAART can cause serious mitochondrial toxicities. One of the most frequent adverse events is lipoatrophy, which is the loss of subcutaneous fat in the face, arms, buttocks, and/or legs as an adverse reaction to nucleoside reverse transcriptase inhibitors. The clinical symptoms of lipoatrophy resemble those of inherited mitochondrial diseases, which suggest that host mitochondrial genotype may play a role in susceptibility. We analyzed the association between mitochondrial haplogroup and severity of lipoatrophy in HIV-infected European American patients on HAART in the Multicenter AIDS cohort Study and found that mitochondrial haplogroup H was strongly associated with increased atrophy [arms: P = 0.007, odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.17 to 2.69; legs: P = 0.037, OR = 1.54, 95% CI = 1.03 to 2.31; and ...
TY - JOUR. T1 - Alterations of mitochondrial DNA in common diseases and disease states. T2 - Aging, neurodegeneration, heart failure, diabetes and cancer. AU - Kang, Dongchon. AU - Hamasaki, Naotaka. PY - 2005/1/1. Y1 - 2005/1/1. N2 - It has long been considered that mitochondrial DNA disease is a rare genetic disorder causing neuromyopathy. However, alterations of mitochondrial DNA recently have been recognized to play an important role in the pathogenesis of so-called common diseases such as heart failure, diabetes, and cancer. Although some of these alterations are inherited, more and more attention is being focused on the accumulation of mitochondrial DNA mutations in somatic cells, particularly terminally differentiated cells such as cardiomyocytes and neurons that occurs with age. Mitochondrial DNA is more vulnerable to alteration than nuclear DNA, mainly for two reasons. First, mitochondria are a major source of intracellular reactive oxygen species (ROS). Therefore mitochondrial DNA is ...
We had previously found that 6-month survival in sepsis patients was significantly associated with platelet COX quantity [4]. However, 1-month survival is a more frequently used parameter in critically ill patients; and we have found that this parameter is also significantly associated with platelet COX quantity. We had previously observed that COX levels can be determined by mtDNA genetic background [6], and other investigators showed that mtDNA haplogroups modified 6-month survival [9]. Here we show that the mtDNA haplogroup determines the platelet COX quantity in sepsis patients and that those patients from the JT mtDNA haplogroup had higher survival rate than those from other mtDNA haplogroups.. The JT mtDNA haplogroup is defined by polymorphisms in nucleotide positions m.4216T , C/MT-ND1, m.11251A , G/MT-ND4, m.15452C , A/MT-CYB and m.16126T , C/MT-DLOOP. The last polymorphism is located in the control region, out of any important sequence for the regulation of mtDNA replication and ...
Clinical presentation of the patients with mitochondrial DNA depletion is quite diverse and is suggestive of genetic heterogeneity. Autosomal recessive inheritance of the disease appears likely, thus implying the nuclear origin of the disease. This has been demonstrated recently in large families wi …
We have analyzed nucleotide sequence variation in an approximately 900-base pair region of the human mitochondrial DNA molecule encompassing the heavy strand origin of replication and the D-loop. Our analysis has focused on nucleotide sequences available from seven humans. Average nucleotide diversity among the sequences is 1.7%, several-fold higher than estimates from restriction endonuclease site variation in mtDNA from these individuals and previously reported for other humans. This disparity is consistent with the rapidly evolving nature of this noncoding region. However, several instances of convergent or parallel gain and loss of restriction sites due to multiple substitutions were observed. In addition, other results suggest that restriction site (as well as pairwise sequence) comparisons may underestimate the total number of substitutions that have occurred since the divergence of two mtDNA sequences from a common ancestral sequence, even at low levels of divergence. This emphasizes the ...
There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA) diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G|A and m.14484T|C occur at higher frequency than expected by change in the Galician (northwest Spain) patients carrying haplogroup J lineages (Fishers Exact test, P-value | 0.01). The assay performs well in mixture experiments of wild:mutant DNAs that emulate heteroplasmic conditions in
To construct maternal phylogeny and prehistoric dispersals of modern human being in the Indian sub continent, a diverse subset of 641 complete mitochondrial DNA (mtDNA) genomes belonging to macrohaplogroup M was chosen from a total collection of 2,783 control-region sequences, sampled from 26 selected tribal populations of India. On the basis of complete mtDNA sequencing, we identified 12 new haplogroups - M53 to M64; redefined/ascertained and characterized haplogroups M2, M3, M4, M5, M6, M8′C′Z, M9, M10, M11, M12-G, D, M18, M30, M33, M35, M37, M38, M39, M40, M41, M43, M45 and M49, which were previously described by control and/or coding-region polymorphisms. Our results indicate that the mtDNA lineages reported in the present study (except East Asian lineages M8′C′Z, M9, M10, M11, M12-G, D ) are restricted to Indian region.The deep rooted lineages of macrohaplogroup M suggest in-situ origin of these haplogroups in India. Most of these deep rooting lineages are represented by multiple ...
Abstract Genetic studies of the distribution of mitochondrial DNA (mtDNA) haplogroups in human populations residing within the Carpathian Mountain range have been scarce. We present an analysis of mtDNA haplogroup composition of the Boykos, Hutsuls, and Lemkos, three population groups of the Carpathian highlands. In our study Hutsuls had the highest frequency of subhaplogroup H1 in central and eastern Europe. Lemkos shared the highest frequency of haplogroup I ever reported and the highest frequency of haplogroup M* in the region. MtDNA haplogroup frequencies in Boykos were different from most modern European populations. We interpreted these unique mtDNA frequencies to be evidence of diverse and dynamic population histories in the Carpathian highland region. ...
Mitochondrial diseases include a group of maternally inherited genetic disorders caused by mutations in mtDNA. In most of these patients, mutated mtDNA coexists with wild-type mtDNA, a situation known as mtDNA heteroplasmy. Here, we report on a strategy toward preventing germline transmission of mitochondrial diseases by inducing mtDNA heteroplasmy shift through the selective elimination of mutated mtDNA. As a proof of concept, we took advantage of NZB/BALB heteroplasmic mice, which contain two mtDNA haplotypes, BALB and NZB, and selectively prevented their germline transmission using either mitochondria-targeted restriction endonucleases or TALENs. In addition, we successfully reduced human mutated mtDNA levels responsible for Leber?s hereditary optic neuropathy (LHOND), and neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), in mammalian oocytes using mitochondria-targeted TALEN (mito-TALENs). Our approaches represent a potential therapeutic avenue for preventing the ...
article{39c3420c-566c-4f24-879b-c3929d10ccd7, abstract = {It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed, significant increased risks of CLL (n=102) with increasing mtDNA ...
Understanding the mechanisms governing transcription of the mammalian mitochondrial DNA genome may offer the possibility of novel treatments for human diseases of mitochondrial dysfunction. In an Advanced Online Publication in Nature Genetics, Falkenberg et al. report the characterization of two proteins that behave as transactivating factors to regulate mitochondrial DNA transcription (Nature Genetics, 17 June 2002, DOI:10.1038/ng909). They performed a sequence homology search to discover two genes (TFB1M and TFB2M) that resemble the yeast Mtf1 protein and bacterial rRNA dimethyltransferases. The two proteins are ubiquitously expressed and are localized in the mitochondria. Both of these mitochondrial proteins can drive mitochondrial DNA transcription in vitroin the presence of mitochondrial RNA polymerase (POLRMT) and transcription factor A (TFAM). ...
Nutrition during early childhood is linked to metabolic programming. We hypothesized that breastfeeding has long-term consequences on the energy metabolism exemplified by mitochondrial DNA (mtDNA). As part of the third cycle of the Flemish Environment and Health Study (FLEHSIII) cohort, 303 adolescents aged 14-15 years were included. We associated breastfeeding and blood mtDNA content 14-15 years later while adjusting for confounding variables. Compared with non-breastfed adolescents, mtDNA content was 23.1% (95%CI: 4.4-45.2; p = 0.013) higher in breastfed adolescents. Being breastfed for 1-10 weeks, 11-20 weeks, and |20 weeks, was associated with a higher mtDNA content of respectively 16.0% (95%CI: −7.1-44.9; p = 0.191), 23.5% (95%CI: 0.8-51.3; p = 0.042), and 31.5% (95%CI: 4.3-65.7; p = 0.021). Our study showed a positive association between breastfeeding and mtDNA content in adolescents which gradually increased with longer periods of breastfeeding. Higher mtDNA content may be an underlying
Haplogroup L1 is believed to have appeared approximately 110,000 to 170,000 years ago.[citation needed] Haplogroup L1 is a daughter of L1-6 and genetic marker changes are 3666, 7055, 7389, 13789, 14178 and 14560. Although it is typically used to denote a group of lineages found within Africa, L1 is sometimes referred to as haplogroup L1-6. The latter is the macrohaplogroup that includes the majority of Africa-based clades and all haplogroups centered outside of the continent. Haplogroup L1-6 is the macrohaplogroup that includes subclades L1, L2, L4, L5, L6, and also L3, which gave rise to the two non-African haplogroups M and N. Haplogroup L1-6 and its only sibling haplogroup L0 are united by the matrilineal most recent common ancestor, (MRCA) of all living humans, Mitochondrial Eve. The existence of these two lineages, implies that Mitochondrial Eve had at least two daughters, one of whom is the maternal common ancestor of haplogroup L1-6 lineages.[citation needed] ...
The mechanisms by which paternal inheritance of mitochondrial DNA (mtDNA) (paternal leakage) and, subsequently, recombination of mtDNA are prevented vary in a species-specific manner with one mechanism in common: paternally derived mtDNA is assumed to be vastly outnumbered by maternal mtDNA in the zygote. To date, this dilution effect has only been described for two mammalian species, human and mouse. Here, we estimate the mtDNA content of chinook salmon oocytes to evaluate the dilution effect operating in another vertebrate; the first such study outside a mammalian system. Employing real-time PCR, we determined the mtDNA content of chinook salmon oocytes to be 3.2 × 109±1.0 × 109, and recently, we determined the mtDNA content of chinook salmon sperm to be 5.73±2.28 per gamete. Accordingly, the ratio of paternal-to-maternal mtDNA if paternal leakage occurs is estimated to be 1:5.5 × 108. This contribution of paternal mtDNA to the overall mtDNA pool in salmon zygotes is three to five orders of
The study presents South American mitochondrial DNA (mtDNA) data from selected north (N = 98), central (N = 193) and south (N = 47) Argentinean populations. Sequence analysis of the complete mtDNA con
During the last few years, mitochondrial DNA has attained much attention as a modulator of immune responses. Due to common evolutionary origin, mitochondrial DNA shares various characteristic features with DNA of bacteria, as it consists of a remarkable number of unmethylated DNA as 2′-deoxyribose cytidine-phosphate-guanosine (CpG) islands. Due to this particular feature, mitochondrial DNA seems to be recognized as a pathogen-associated molecular pattern by the innate immune system. Under the normal physiological situation, mitochondrial DNA is enclosed in the double membrane structure of mitochondria. However, upon pathological conditions, it is usually released into the cytoplasm. Growing evidence suggests that this cytosolic mitochondrial DNA induces various innate immune signaling pathways involving NLRP3, toll-like receptor 9, and stimulator of interferon genes (STING) signaling, which participate in triggering downstream cascade and stimulating to produce effector molecules. Mitochondrial DNA is
Holyoake, A. J., McHugh, Patrick C, Wu, M., OCarroll, S., Benny, P., Sin, I. L. and Sin, F. Y. T. (2002) Research of single mitochondrial nucleotide substitutions in male infertility should consider human mitochondrial haplogroups - Reply. International Journal of Andrology, 25 (6). p. 374. ISSN 0105-6263 Metadata only available from this repository ...
TY - JOUR. T1 - Mitochondrial DNA mutations cause resistance to opening of the permeability transition pore. AU - Mott, Justin L.. AU - Zhang, Dekui. AU - Chang, Shin Wen. AU - Zassenhaus, H. Peter. N1 - Funding Information: We thank Dr. T. Heyduk for his assistance with fluorescence assays. We gratefully acknowledge grant support from the National Institutes of Health (NHLBI and NIA) and the American Heart Association to HPZ and from the American Diabetes Association to JLM.. PY - 2006/5. Y1 - 2006/5. N2 - The age-related accumulation of mitochondrial DNA mutations has the potential to impair organ function and contribute to disease. In support of this hypothesis, accelerated mitochondrial mutagenesis is pathogenic in the mouse heart, and there is an increase in myocyte apoptosis. The current study sought to identify functional alterations in cell death signaling via mitochondria. Of particular interest is the mitochondrial permeability transition pore, opening of which can initiate cell death, ...
Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from
Mitochondria are the organelles responsible for producing the majority of a cells ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend ...
Sharma et al. BMC Genetics (2015) 16:73 DOI 10.1186/s12863-015-0221-0. ^BMC Genetics. RESEARCH ARTICLE. Open Access. Genetic diversity and relationship of Indian cattle inferred from microsatellite and mitochondrial DNA markers. CrossMark. Rekha Sharma , Amit Kishore, Manishi Mukesh, Sonika Ahlawat, Avishek Maitra, Ashwni Kumar Pandey and Madhu Sudan Tantia. Abstract. Background: Indian agriculture is an economic symbiosis of crop and livestock production with cattle as the foundation. Sadly, the population of indigenous cattle (Bos indicus) is declining (8.94 % in last decade) and needs immediate scientific management. Genetic characterization is the first step in the development of proper management strategies for preserving genetic diversity and preventing undesirable loss of alleles. Thus, in this study we investigated genetic diversity and relationship among eleven Indian cattle breeds using 21 microsatellite markers and mitochondrial D loop sequence.. Results: The analysis of autosomal DNA ...
The mitochondrial genome is maternally inherited and harbors 37 genes in a circular molecule of approximately 16.6 kb that is present in hundreds to thousands of copies per cell [1] and has accumulated mutations at a rate at least an order of magnitude higher than its nuclear counterpart [2, 3]. Frequently, more than one mtDNA variant is present in the same individual, a phenomenon called heteroplasmy [4]. The mitochondrial genome is implicated in hundreds of diseases (over 200 catalogued at [5] as of mid-2010) with the majority of them caused by point mutations [6]. Multiple mtDNA mutations might also predispose one to common metabolic and neurological diseases of advanced age, such as diabetes as well as Parkinsons and Alzheimers diseases [7]. Additionally, mtDNA mutations appear to have a role in cancer etiology [8]. Many disease-causing mtDNA variants are heteroplasmic and their clinical manifestation depends on the relative proportion of mutant versus normal mitochondrial genomes [7, 9, ...
Mutations in genes encoding components of the mitochondrial DNA (mtDNA) replication machinery cause mtDNA depletion syndromes (MDSs), which associate ocular features with severe neurological syndromes. Here, we identified heterozygous missense mutations in single-strand binding protein 1 (SSBP1) in 5 unrelated families, leading to the R38Q and R107Q amino acid changes in the mitochondrial single-stranded DNA-binding protein, a crucial protein involved in mtDNA replication. All affected individuals presented optic atrophy, associated with foveopathy in half of the cases. To uncover the structural features underlying SSBP1 mutations, we determined a revised SSBP1 crystal structure. Structural analysis suggested that both mutations affect dimer interactions and presumably distort the DNA-binding region. Using patient fibroblasts, we validated that the R38Q variant destabilizes SSBP1 dimer/tetramer formation, affects mtDNA replication, and induces mtDNA depletion. Our study showing that mutations in ...
The mitochondrial DNA (mtDNA) is highly variable, containing large numbers of pathogenic mutations and neutral polymorphisms. The spectrum of homoplasmic mtDNA variation was characterized in 730 subjects and compared with known pathogenic sites. The frequency and distribution of variants in protein coding genes were inversely correlated with conservation at the amino acid level. Analysis of tRNA secondary structures indicated a preference of variants for the loops and some acceptor stem positions. This comprehensive overview of mtDNA variants distinguishes between regions and positions which are likely not critical, mainly conserved regions with pathogenic mutations and essential regions containing no mutations at all. ...
In this large prospective study of a general population of Northern European descent, no evidence was found for consistent and robust associations between mitochondrial haplogroups and risk of ischemic cardiovascular disease, morbidity from other causes, or mortality. In contrast, several smaller case-control studies have shown associations between mitochondrial haplogroups and myocardial infarction, cerebral infarction, cancer, diabetes mellitus, and neurodegenerative diseases.18-36. The Asian N9b haplogroup (defined by polymorphisms at positions mt5147 and mt16519) has been reported to protect against myocardial infarction in Japanese men (odds ratio [95% CI], 0.2 [0.1 to 0.5]; 920 cases/522 controls) but not in Japanese women (695 cases/434 controls).19 It has been speculated that this reduction in risk of myocardial infarction could be due to a reduction in the production of superoxide and other reactive oxygen species associated with this particular haplogroup19 that thus might confer ...
Mammalian mitochondrial DNA (mtDNA) resides in compact nucleoids, where it is replicated and transcribed into long primary transcripts processed to generate rRNAs, tRNAs, and mRNAs encoding 13 proteins. This situation differs from bacteria and eukaryotic nucleoli, which have dedicated rRNA transcrip …
Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant prognostic and diagnostic markers are still missing. At the same time mitochondrial DNA mutations have been reported in many types of cancer during the last two decades. It is therefore very likely that the mitochondrial genotype is one of the cancer susceptibility factors. To investigate the presence of mtDNA somatic mutations and distribution of inherited polymorphisms in endometrial adenocarcinoma patients we analyzed the D-loop sequence of cancer samples and their corresponding normal tissues and moreover performed mitochondrial haplogroup analysis. We detected 2 somatic mutation and increased incidence of mtDNA polymorphisms, in particular 16223C (80% patients, p = 0.005), 16126C (23%, p = 0.025) and 207A (19%, p = 0.027). Subsequent statistical analysis revealed that
Three pairs of parental (ρ+) and established mitochondrial DNA depleted (ρ0) cells, derived from bone, lung and muscle were used to verify the influence of the nuclear background and the lack of efficient mitochondrial respiratory chain on antioxidant defences and homeostasis of intracellular reactive oxygen species (ROS). Mitochondrial DNA depletion significantly lowered glutathione reductase activity, glutathione (GSH) content, and consistently altered the GSH2 : oxidized glutathione ratio in all of the ρ0 cell lines, albeit to differing extents, indicating the most oxidized redox state in bone ρ0 cells. Activity, as well as gene expression and protein content, of superoxide dismutase showed a decrease in bone and muscle ρ0 cell lines but not in lung ρ0 cells. GSH peroxidase activity was four times higher in all three ρ0 cell lines in comparison to the parental ρ+, suggesting that this may be a necessary adaptation for survival without a functional respiratory chain. Taken together, ...