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1.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 851-855, 2020 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-33047718

RESUMO

OBJECTIVE: Mitochondrial deoxyribonucleic acid (mtDNA) 8344 A>G (m.8344A>G) mutation is the common mutation associated with mitochondrial myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. Herein we report a rare case with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes/MERRF/Leigh (MELAS/MERRF/Leigh) overlap syndrome caused by m.8344A>G mutation. METHODS: The clinical and imaging data of the patient were collected and an open muscle biopsy was carried out. We further employed molecular genetic analyses to detect mtDNA mutation in the proband and his mother. And then a clinical and neuroimaging follow-up was performed. RESULTS: This patient was a 25-year-old male, who developed exercise intolerance since the age of 6. At age 10, he suffered from acute episodes of hemianopia, and cranial magnetic resonance imaging (MRI) showed occipital stroke-like lesions and cranial magnetic resonance spectroscopy (MRS) revealed a lactate peak corresponding to the lesion. After that the patient presented slowly progressive psychomotor decline. He had myoclonic seizures and cerebellar ataxia since the age of 12. At age 21, he was admitted to our hospital because of confusion and cranial MRI revealed symmetrical lesions in bilateral posterior putamen, thalami and midbrain. Then repeated MRI showed progression of original lesions and new frontal multiple stroke-like lesions. Symptomatic and rehabilitation treatment relieved his condition. Follow-up cranial MRI at age 24 showed the lesions in basal ganglia and thalami diminished, and the midbrain lesions even completely vanished. Muscle pathology indicated the presence of numerous scattered ragged-red fibers (RRF), suggestive of a mitochondrial disorder. Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) detected the m.8344A>G mutation of the MT-TK gene encoding mitochondrial transfer RNA for lysine in the patient's blood. Next generation sequencing (NGS) of the whole mitochondrial genome identified that the proportion of m.8344A>G was 90%, and no other mtDNA mutation was detected. Sanger sequencing further identified this mutation both in the proband and his mother's blood, although the mutation load was much lower in his mother's blood with approximately 10% heteroplasmy. CONCLUSION: The present study is the first to describe a patient with m.8344A>G mutation in association with the MELAS/MERRF/Leigh overlap syndrome, which expands the phenotypic spectrum of the m.8344A>G mutation.


Assuntos
Acidose Láctica , Acidente Vascular Cerebral , Adulto , Criança , DNA Mitocondrial/genética , Humanos , Masculino , Encefalomiopatias Mitocondriais , Mutação , Adulto Jovem
2.
Nat Commun ; 11(1): 4048, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873779

RESUMO

Pleistocene glacial-interglacial cycles are correlated with dramatic temperature oscillations. Examining how species responded to these natural fluctuations can provide valuable insights into the impacts of present-day anthropogenic climate change. Here we present a phylogeographic study of the extinct American mastodon (Mammut americanum), based on 35 complete mitochondrial genomes. These data reveal the presence of multiple lineages within this species, including two distinct clades from eastern Beringia. Our molecular date estimates suggest that these clades arose at different times, supporting a pattern of repeated northern expansion and local extirpation in response to glacial cycling. Consistent with this hypothesis, we also note lower levels of genetic diversity among northern mastodons than in endemic clades south of the continental ice sheets. The results of our study highlight the complex relationships between population dispersals and climate change, and can provide testable hypotheses for extant species expected to experience substantial biogeographic impacts from rising temperatures.


Assuntos
Mudança Climática , Especiação Genética , Genoma Mitocondrial , Mastodontes/genética , Animais , DNA Antigo/análise , DNA Antigo/isolamento & purificação , DNA Mitocondrial/genética , DNA Mitocondrial/isolamento & purificação , Feminino , Fósseis , Masculino , Filogeografia
3.
Korean J Parasitol ; 58(4): 451-456, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32871639

RESUMO

This is a report of 2 cases of human hydatidosis caused by Echinococcus ortleppi in Vietnam. The patients were a 12-year-old male (case 1) having a cyst of 10.0×9.0 cm size in the lung and a 50-year-old female with a 3.0×3.3 cm-sized cyst in the heart. Eosinophilia was 33.7% in the male and 45.8% in the female patient. C-reactive protein was increased to 16.5 mg/L in the male and 18.2 mg/L in the female. Both patients were positive for ELISA at OD=2.5 and 3.1, respectively. Echinococcus protoscolices were collected from the cysts by amniocentesis and surgery. The protoscolices were identified as E. ortleppi by morphology and analysis of mitochondrial NADH dehydrogenase 1 (nad1) gene sequence. Both patients were cured by surgical resection of the hydatid cyst combined with albendazole medication. The E. ortleppi infection in lung is the second report, and the other in the heart is the first in Vietnam.


Assuntos
Equinococose/diagnóstico , Equinococose/parasitologia , Albendazol/uso terapêutico , Animais , Biomarcadores , Proteína C-Reativa , Criança , DNA de Helmintos/genética , DNA Mitocondrial/genética , Equinococose/cirurgia , Echinococcus/genética , Echinococcus/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Feminino , Cardiopatias , Humanos , Pneumopatias Parasitárias , Masculino , Pessoa de Meia-Idade , NADH Desidrogenase/genética , Análise de Sequência de DNA , Vietnã
4.
Nat Commun ; 11(1): 3868, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747648

RESUMO

Archaeological research documents major technological shifts among people who have lived in the southern tip of South America (South Patagonia) during the last thirteen millennia, including the development of marine-based economies and changes in tools and raw materials. It has been proposed that movements of people spreading culture and technology propelled some of these shifts, but these hypotheses have not been tested with ancient DNA. Here we report genome-wide data from 20 ancient individuals, and co-analyze it with previously reported data. We reveal that immigration does not explain the appearance of marine adaptations in South Patagonia. We describe partial genetic continuity since ~6600 BP and two later gene flows correlated with technological changes: one between 4700-2000 BP that affected primarily marine-based groups, and a later one impacting all <2000 BP groups. From ~2200-1200 BP, mixture among neighbors resulted in a cline correlated to geographic ordering along the coast.


Assuntos
DNA Antigo/análise , Fósseis , Fluxo Gênico , Genoma Humano/genética , Migração Humana , Arqueologia/métodos , Argentina , Osso e Ossos/metabolismo , Chile , DNA Mitocondrial/classificação , DNA Mitocondrial/genética , Variação Genética , Geografia , Humanos , Filogenia , Datação Radiométrica/métodos , Análise de Sequência de DNA/métodos , Dente/metabolismo
5.
PLoS Negl Trop Dis ; 14(8): e0008480, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813714

RESUMO

Clonorchiasis is a neglected tropical disease caused by the Chinese liver fluke, Clonorchis sinensis, and is often associated with a malignant form of bile duct cancer (cholangiocarcinoma). Although some aspects of the epidemiology of clonorchiasis are understood, little is known about the genetics of C. sinensis populations. Here, we conducted a comprehensive genetic exploration of C. sinensis from endemic geographic regions using complete mitochondrial protein gene sets. Genomic DNA samples from C. sinensis individuals (n = 183) collected from cats and dogs in China (provinces of Guangdong, Guangxi, Hunan, Heilongjiang and Jilin) as well as from rats infected with metacercariae from cyprinid fish from the Russian Far East (Primorsky Krai region) were deep sequenced using the BGISEQ-500 platform. Informatic analyses of mitochondrial protein gene data sets revealed marked genetic variation within C. sinensis; significant variation was identified within and among individual worms from distinct geographical locations. No clear affiliation with a particular location or host species was evident, suggesting a high rate of dispersal of the parasite across endemic regions. The present work provides a foundation for future biological, epidemiological and ecological studies using mitochondrial protein gene data sets, which could aid in elucidating associations between particular C. sinensis genotypes/haplotypes and the pathogenesis or severity of clonorchiasis and its complications (including cholangiocarcinoma) in humans.


Assuntos
Clonorquíase/parasitologia , Clonorchis sinensis/genética , DNA Mitocondrial/genética , Variação Genética , Animais , China/epidemiologia , Clonorquíase/epidemiologia , Haploidia , Interações Hospedeiro-Parasita , Humanos , Filogenia , Federação Russa/epidemiologia
6.
PLoS One ; 15(8): e0238049, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32834019

RESUMO

Genetics of pigs has been well studied in Europe and Asia, but most of previous studies of molecular phylogeny of Sus scrofa have been based on sequences of both wild and domestic forms. In this study we analysed genetic traits of Sus scrofa from 13 regions in Asia (including previously undisclosed Eastern Caucasus and Trans-Baikal regions) using purely wild boar samples. Mitochondrial control region and Y-chromosome genes (AMELY & USP9Y) were employed to resolve phylogeographic relationships. We discussed spatio-temporal dynamics of wild boar distribution and compared molecular data to morphological and cytogenetic data on wild boar variability and taxonomy. A total of 51 haplotypes were detected in mtDNA control region and five haplotypes were found in combined sequences of Y-chromosome genes. The phylogeography of Asia-wide wild boars supported a hypothesis of migration from South-East Asia to South Asia, followed by migration to East and West Asia. We present a hypothesis about independent dispersal of wild boars into West Asia from South and North-East Asia. Mitochondrial DNA phylogeny generally fits the morphologically based intraspecies taxonomy. Distribution of chromosomal variants of wild boar presently does not show clear correlation with mtDNA clades.


Assuntos
DNA Mitocondrial/genética , Filogeografia , Sus scrofa/genética , Cromossomo Y/genética , Animais , Ásia , Variação Genética
7.
Parasitol Res ; 119(10): 3255-3283, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32856113

RESUMO

Seven new species of Urocleidoides from the gills and skin of nine Neotropical fish hosts (Anostomidae, Parodontidae, and Gymnotidae) are described: Urocleidoides digitabulum n. sp. on Leporinus friderici, Leporinus octofasciatus, and Megaleporinus elongatus (Anostomidae); Urocleidoides solarivaginatus n. sp. on L. friderici, L. octofasciatus, and Leporinus striatus (Anostomidae); Urocleidoides falxus n. sp. and Urocleidoides sapucaiensis n. sp. on M. elongatus; Urocleidoides tenuis n. sp. on Apareiodon piracicabae and Apareiodon affinis (Parodontidae); Urocleidoides sinus n. sp. on L. striatus, Schizodon nasutus, and Schizodon intermedius (Anostomidae); and Urocleidoides uncinus n. sp. on Gymnotus sylvius (Gymnotidae). Urocleidoides paradoxus was also found in this study on L. friderici and included in the phylogenetic analysis. Molecular data (partial 28S rDNA and mitochondrial cytochrome oxidase subunit I) were obtained for U. digitabulum n. sp., U. tenuis n. sp., U. sinus n. sp., and U. uncinus n. sp. The identification of Urocleidoides is amended herein to include all taxonomic modifications observed in this genus over time and add new characteristics observed in the species in the present study. Phylogenetic analysis revealed Urocleidoides digitabulum n. sp. and Urocleidoides sinus n. sp. (parasites of anostomids) closely related in the tree topologies. Furthermore, the new species described herein parasitized phylogenetically distant host species (Characiformes and Gymnotiformes), suggesting the effect of the dynamic process of ecological fitting.


Assuntos
Caraciformes/parasitologia , Gimnotiformes/parasitologia , Platelmintos/isolamento & purificação , Animais , Brasil , DNA Mitocondrial/genética , DNA Ribossômico/genética , Peixes , Brânquias/parasitologia , Especificidade de Hospedeiro , Filogenia , Platelmintos/classificação , Platelmintos/genética , RNA Ribossômico 28S/genética
8.
Parasitol Res ; 119(10): 3327-3338, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32789533

RESUMO

The evolutionary history of Acanthamoeba has been substantially resolved by the 18S rDNA phylogeny which made it possible to delimit the main lines associated with some classical species. Some of them have proven to be polyphyletic, but the inappropriate use of treating under the same names unrelated strains persists. In this study, phylogenies based on the complete genes of nuclear and mitochondrial rDNA were compared, in order to verify the congruence of the different lines. Various groups can thus be identified, some of which associated with the type strains of given species. Recognizing them only by their species names would significantly reduce the current confusion, in addition to logically following basic taxonomic rules. In this manner, the well-known polyphyletic taxa A. castellanii and A. polyphaga, are restricted to the two lines specified by their type strains, while other widely used strains like Neff and Linc-AP1 that are often confused with the previous ones, can be assigned to their own lines. New species are potentially present in other groups and additional efforts are needed to delimit them.


Assuntos
Acanthamoeba/classificação , Filogenia , Acanthamoeba/genética , Animais , DNA Mitocondrial/genética , DNA Ribossômico/genética , Genes de Protozoários/genética , Genótipo
9.
Parasitol Res ; 119(10): 3285-3296, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32812144

RESUMO

The taxonomy of Hysterothylacium genus in Mediterranean waters remains incomplete and unresolved. The aim of the current study was to investigate the morphological and molecular identification of selected species of Hysterothylacium larvae in marine fish from the Tunisian Mediterranean coasts. A total of 192 marine fish samples were examined. In total, thirty-seven third-stage larvae of Hysterothylacium were morphologically identified as Hysterothylacium type V. In the present study, representatives of this type from the Mediterranean Sea were genetically characterized for the first time by sequencing the rDNA ITS (ITS1-5.8S-ITS2) regions and mtDNA cox2 gene. This study represents the first report of Hysterothylacium type V from the Mediterranean Sea. We also report Mullus barbatus, M. surmuletus, and Pagellus erythrinus as new hosts for this larval type. Based upon molecular and phylogenetic analyses considering the rDNA ITS regions, the Hysterothylacium type V described here was classified as a new genotype, named Genotype B. The valid genetic data of the described Hysterothylacium type V in the present study can be used to establish the phylogenetic relationships among Hysterothylacium species from the Mediterranean Sea and worldwide for future research.


Assuntos
Infecções por Ascaridida/veterinária , Ascaridoidea/classificação , Ascaridoidea/crescimento & desenvolvimento , Doenças dos Peixes/parasitologia , Peixes/parasitologia , Animais , Infecções por Ascaridida/parasitologia , Ascaridoidea/anatomia & histologia , Ascaridoidea/genética , DNA Mitocondrial/genética , DNA Espaçador Ribossômico/genética , Peixes/classificação , Genes de Helmintos/genética , Genótipo , Larva/anatomia & histologia , Larva/classificação , Larva/genética , Larva/crescimento & desenvolvimento , Mar Mediterrâneo , Filogenia
10.
Parasitol Res ; 119(10): 3339-3345, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32827102

RESUMO

Genetic variations in the 18S ribosomal DNA (18S), 28S ribosomal DNA (28S), second internal transcribed spacer of ribosomal DNA (ITS2), and mitochondrial cytochrome c oxidase subunit 1 (cox1) of Neoschoengastia gallinarum collected from subtropical China were examined. First, a portion of the 18S (p18S), a portion of the 28S (p28S), and the complete ITS2 were separately amplified from individual mites and sequenced. The lengths of the sequences of p18S, p28S, and ITS2 were found to be 1379 bp, 3465~3468 bp, and 200 bp, respectively. The intraspecific sequence variation was 0~0.1% for p28S and 0~1.6% for ITS2, though no variation was observed for p18S, suggesting conservation of rDNA sequences. Second, a portion of the mitochondrial cox1 gene (pcox1) of N. gallinarum was analyzed. The length of the pcox1 sequence is 460 bp, and two distinct groups were observed in N. gallinarum. All pcox1 sequences in group I were identical, and there was only one nucleotide transition observed in group II; however, 7.0~7.2% variations between the two groups were observed, suggesting that two genotypes of N. gallinarum: genotype I and genotype II. Phylogenetic analyses based on pcox1 sequences indicated that N. gallinarum isolates (genotype I or genotype II) clustered into one branch; according to cox1 sequence analysis of Trombiculidae, Walchia hayashii is the closest species. The present study shows that ITS2 rDNA sequence can act as marker for the identification of N. gallinarum samples. Furthermore, analysis of the mitochondrial pcox1 sequence suggests the existence of two genotypes, which has implications for further studies of the ecology and population genetic structures of N. gallinarum.


Assuntos
Ciclo-Oxigenase 1/genética , DNA Ribossômico/genética , Trombiculidae/genética , Animais , China , DNA Mitocondrial/genética , Variação Genética , Genótipo , Filogenia , Análise de Sequência de DNA , Trombiculidae/classificação
11.
Gene ; 761: 145047, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32783993

RESUMO

Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.


Assuntos
Neoplasias da Mama/genética , Variações do Número de Cópias de DNA/genética , DNA Mitocondrial/genética , Adulto , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos/genética , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Mitocôndrias/genética
12.
PLoS One ; 15(8): e0237235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785256

RESUMO

Mitochondrial DNA copy number (mtDNAcn) is a putative biomarker of oxidative stress and biological aging. Modifiable factors, including physical activity (PA), avoidance of heavy alcohol use and smoking, and maintaining good mental health, may reduce oxidative stress and promote healthy aging. Yet, limited data exist regarding how these factors are associated with mtDNAcn or whether age, sex or race/ethnicity moderate associations. In this cross-sectional study, we selected 391 adults (183 non-Hispanic White, 110 Black and 98 Hispanic; mean = 67 years) from the VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention) ancillary to the VITAL trial. We estimated associations between lifestyle and behavioral factors (PA, alcohol consumption, cigarette smoking and depression) and log-transformed mtDNAcn using multivariable linear regression models. MtDNAcn was not correlated with chronological age; women had ~17% higher mtDNAcn compared to men. There were no significant associations between PA measures (frequency, amount or intensity) or alcohol consumption with mtDNAcn. Cigarette smoking (per 5 pack-years) was significantly associated with mtDNAcn (percent difference = -2.9% (95% confidence interval (CI) = -5.4%, -0.4%)); a large contrast was observed among heavy vs. non-smokers (≥30 vs. 0 pack-years): percent difference = -28.5% (95% CI = -44.2%, -8.3%). The estimate of mtDNAcn was suggestively different for past vs. no depression history (percent difference = -15.1% 95% CI = -30.8%, 4.1%), but this difference was not statistically significant. The association between smoking and log-mtDNAcn varied by sex and race/ethnicity; it was stronger in men and Black participants. While chance findings cannot be excluded, results from this study support associations of smoking, but not chronological age, with mtDNAcn and suggest nuanced considerations of mtDNAcn as indicative of varying oxidative stress states vs. biological aging itself.


Assuntos
Variações do Número de Cópias de DNA , DNA Mitocondrial/genética , Estilo de Vida , Idoso , Envelhecimento , Consumo de Bebidas Alcoólicas/genética , Fumar Cigarros/genética , Estudos Transversais , Depressão/genética , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
PLoS One ; 15(8): e0237249, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804938

RESUMO

Biological control (biocontrol) as a component of pest management strategies reduces reliance on synthetic chemicals, and seemingly offers a natural approach that minimizes environmental impact. However, introducing a new organism to new environments as a classical biocontrol agent can have broad and unanticipated biodiversity effects and conservation consequences. Nematodes are currently used in a variety of commercial biocontrol applications, including the use of Phasmarhabditis hermaphrodita as an agent targeting pest slug and snail species. This species was originally discovered in Germany, and is generally thought to have European origins. P. hermaphrodita is sold under the trade name Nemaslug®, and is available only in European markets. However, this nematode species was discovered in New Zealand and the western United States, though its specific origins remained unclear. In this study, we analyzed 45 nematode strains representing eight different Phasmarhabditis species, collected from nine countries around the world. A segment of nematode mitochondrial DNA (mtDNA) was sequenced and subjected to phylogenetic analyses. Our mtDNA phylogenies were overall consistent with previous analyses based on nuclear ribosomal RNA (rRNA) loci. The recently discovered P. hermaphrodita strains in New Zealand and the United States had mtDNA haplotypes nearly identical to that of Nemaslug®, and these were placed together in an intraspecific monophyletic clade with high support in maximum likelihood and Bayesian analyses. We also examined bacteria that co-cultured with the nematode strains isolated in Oregon, USA, by analyzing 16S rRNA sequences. Eight different bacterial genera were found to associate with these nematodes, though Moraxella osloensis, the bacteria species used in the Nemaslug® formulation, was not detected. This study provided evidence that nematodes deriving from the Nemaslug® biocontrol product have invaded countries where its use is prohibited by regulatory agencies and not commercially available.


Assuntos
Espécies Introduzidas , Filogenia , Rabditídios/genética , Animais , DNA Mitocondrial/genética , Europa (Continente) , Nova Zelândia , América do Norte , Controle Biológico de Vetores , RNA Ribossômico 16S/genética , Rabditídios/isolamento & purificação
14.
DNA Cell Biol ; 39(8): 1449-1457, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32609007

RESUMO

Kearns-Sayre Syndrome (KSS) is a severe mitochondrial disorder involving the central nervous system, eyes, ears, skeletal muscles, and heart. The mitochondrial DNA (mtDNA) rearrangements, especially the deletions, are present in almost all KSS patients and considered as the disease-causing factor. However, the size and position of mtDNA deletions are distinct in different individuals. In this study, we report the case of a pair of Chinese twins with KSS. The twin patients revealed typical KSS clinical symptoms, including heart block, bilateral sensorineural hearing loss, progressive external ophthalmoplegia, exercise intolerance, proximal limb weakness, and endocrine disorders. Using long-range polymerase chain reactions (long-range PCR) and next-generation sequencing (NGS), the genetic features of the twin patients were investigated. A large 6600 bp mtDNA deletion, ranging from position 8702 to 15,302, was detected in both patients. To our knowledge, this kind of mtDNA deletion has never been described previously. Our study enriched the mutation spectrum of KSS and showed that NGS is a powerful tool for detecting mtDNA large variants.


Assuntos
DNA Mitocondrial/genética , Doenças em Gêmeos/genética , Síndrome de Kearns-Sayre/genética , Oftalmoplegia Externa Progressiva Crônica/genética , Sistema Nervoso Central/patologia , Criança , Cromossomos/genética , Doenças em Gêmeos/patologia , Orelha/patologia , Olho/patologia , Deleção de Genes , Predisposição Genética para Doença , Coração/fisiopatologia , Humanos , Síndrome de Kearns-Sayre/patologia , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Mutação/genética , Oftalmoplegia Externa Progressiva Crônica/patologia , Fenótipo
15.
PLoS One ; 15(6): e0234385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603327

RESUMO

Utilising a reconstructed ancestral mitochondrial genome of a clade to design hybridisation capture baits can provide the opportunity for recovering mitochondrial sequences from all its descendent and even sister lineages. This approach is useful for taxa with no extant close relatives, as is often the case for rare or extinct species, and is a viable approach for the analysis of historical museum specimens. Asiatic linsangs (genus Prionodon) exemplify this situation, being rare Southeast Asian carnivores for which little molecular data is available. Using ancestral capture we recover partial mitochondrial genome sequences for seven banded linsangs (P. linsang) from historical specimens, representing the first intraspecific genetic dataset for this species. We additionally assemble a high quality mitogenome for the banded linsang using shotgun sequencing for time-calibrated phylogenetic analysis. This reveals a deep divergence between the two Asiatic linsang species (P. linsang, P. pardicolor), with an estimated divergence of ~12 million years (Ma). Although our sample size precludes any robust interpretation of the population structure of the banded linsang, we recover two distinct matrilines with an estimated tMRCA of ~1 Ma. Our results can be used as a basis for further investigation of the Asiatic linsangs, and further demonstrate the utility of ancestral capture for studying divergent taxa without close relatives.


Assuntos
Genoma Mitocondrial , Viverridae/genética , Animais , Ásia Sudeste , DNA Mitocondrial/genética , DNA Mitocondrial/história , Bases de Dados de Ácidos Nucleicos , Evolução Molecular , Extinção Biológica , Fósseis/história , Especiação Genética , História Antiga , Filogenia , Filogeografia , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade da Espécie , Viverridae/classificação
16.
PLoS Biol ; 18(7): e3000745, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32667908

RESUMO

Mutations create genetic variation for other evolutionary forces to operate on and cause numerous genetic diseases. Nevertheless, how de novo mutations arise remains poorly understood. Progress in the area is hindered by the fact that error rates of conventional sequencing technologies (1 in 100 or 1,000 base pairs) are several orders of magnitude higher than de novo mutation rates (1 in 10,000,000 or 100,000,000 base pairs per generation). Moreover, previous analyses of germline de novo mutations examined pedigrees (and not germ cells) and thus were likely affected by selection. Here, we applied highly accurate duplex sequencing to detect low-frequency, de novo mutations in mitochondrial DNA (mtDNA) directly from oocytes and from somatic tissues (brain and muscle) of 36 mice from two independent pedigrees. We found mtDNA mutation frequencies 2- to 3-fold higher in 10-month-old than in 1-month-old mice, demonstrating mutation accumulation during the period of only 9 mo. Mutation frequencies and patterns differed between germline and somatic tissues and among mtDNA regions, suggestive of distinct mutagenesis mechanisms. Additionally, we discovered a more pronounced genetic drift of mitochondrial genetic variants in the germline of older versus younger mice, arguing for mtDNA turnover during oocyte meiotic arrest. Our study deciphered for the first time the intricacies of germline de novo mutagenesis using duplex sequencing directly in oocytes, which provided unprecedented resolution and minimized selection effects present in pedigree studies. Moreover, our work provides important information about the origins and accumulation of mutations with aging/maturation and has implications for delayed reproduction in modern human societies. Furthermore, the duplex sequencing method we optimized for single cells opens avenues for investigating low-frequency mutations in other studies.


Assuntos
Envelhecimento/genética , Mamíferos/genética , Mitocôndrias/genética , Mutação/genética , Oócitos/metabolismo , Especificidade de Órgãos/genética , Animais , Análise Mutacional de DNA , DNA Mitocondrial/genética , Feminino , Frequência do Gene/genética , Deriva Genética , Células Germinativas/metabolismo , Padrões de Herança/genética , Modelos Logísticos , Masculino , Camundongos , Modelos Genéticos , Taxa de Mutação , Nucleotídeos/genética , Linhagem
17.
Cancer Invest ; 38(7): 375-393, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32673136

RESUMO

mtDNA is the closed circular, ds-DNA present in mitochondria of eukaryotic cells and are inherited maternally. Besides being the power house of the cell, mitochondria are also responsible for the regulation of redox homeostasis, signaling, metabolism, immunity, survival and apoptosis. Lack of a 'Systematic Review' on mtDNA variations and cancers encouraged us to perform the present study. Pubmed', 'Embase' and 'Cochrane Library' databases were searched using keywords 'Mitochondrial DNA' OR 'mtDNA' OR 'mDNA' AND 'polymorphism' AND 'cancer' AND 'risk' to retrieve literature. Polymorphisms occupy first rank among mtDNA variations followed by CNV, MSI, mutations and hold a great potential to emerge as key predictors for human cancers.


Assuntos
DNA Mitocondrial/genética , Neoplasias/genética , Polimorfismo Genético , Feminino , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mutação
18.
PLoS One ; 15(7): e0235856, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649732

RESUMO

Gene editing in large animal models for future applications in translational medicine and food production must be deeply investigated for an increase of knowledge. The mitochondrial transcription factor A (TFAM) is a member of the HMGB subfamily that binds to mtDNA promoters. This gene maintains mtDNA, and it is essential for the initiation of mtDNA transcription. Lately, we generated a new cell line through the disruption of the TFAM gene in bovine fibroblast cells by CRISPR/Cas 9 technology. We showed that the CRISPR/Cas9 design was efficient through the generation of heterozygous mutant clones. In this context, once this gene regulates the mtDNA replication specificity, the study aimed to determine if the post-edited cells are capable of in vitro maintenance and assess if they present changes in mtDNA copies and mitochondrial membrane potential after successive passages in culture. The post-edited cells were expanded in culture, and we performed a growth curve, doubling time, cell viability, mitochondrial DNA copy number, and mitochondrial membrane potential assays. The editing process did not make cell culture unfeasible, even though cell growth rate and viability were decreased compared to control since we observed the cells grow well when cultured in a medium supplemented with uridine and pyruvate. They also exhibited a classical fibroblastoid appearance. The RT-qPCR to determine the mtDNA copy number showed a decrease in the edited clones compared to the non-edited ones (control) in different cell passages. Cell staining with Mitotracker Green and red suggests a reduction in red fluorescence in the edited cells compared to the non-edited cells. Thus, through characterization, we demonstrated that the TFAM gene is critical to mitochondrial maintenance due to its interference in the stability of the mitochondrial DNA copy number in different cell passages and membrane potential confirming the decrease in mitochondrial activity in cells edited in heterozygosis.


Assuntos
Sistemas CRISPR-Cas , Bovinos/genética , Proteínas de Ligação a DNA/genética , Edição de Genes , Proteínas Mitocondriais/genética , Fatores de Transcrição/genética , Animais , Células Cultivadas , Replicação do DNA , DNA Mitocondrial/genética , Fibroblastos/metabolismo , Dosagem de Genes , Mitocôndrias/genética
19.
Gene ; 758: 144962, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32687946

RESUMO

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by the autoimmune inflammation, demyelination, and neurodegeneration. This complex disease develops in genetically predisposed individuals under adverse environmental factors. To date, a large number of MS-associated polymorphic loci of the nuclear genome have been identified; however, their total variability can explain only about 48% of the observed inheritance of MS. Polymorphic variants of the mitochondrial genome and interactions of mitochondrial and nuclear genes (mitonuclear interactions) may be the possible sources of the "missing heritability". We analyzed the association with MS of 10 mitochondrial DNA polymorphisms (m.1719, m.4216, m.4580, m.4917, m.7028, m.9055, m.10398, m.12308, m.13368, m.13708) in DNA of 540 MS patients and 406 healthy individuals. The allele m.9055*G was the only mitochondrial variant associated with MS (Pf = 0.027). To evaluate interactions of mitochondrial and nuclear genomes, we searched for biallelic combinations containing one of 10 mitochondrial variants and one of 35 variants of immune-related nuclear genes. Carriership of mitochondrial variants m.4216, m.4580, or m.13708 in biallelic combinations with variants of nuclear genes IL7R, CLEC16A, CD6, CD86 or PVT1 was associated with MS (Pf = 0.0036-0.00030). We identified epistatic interaction between components of a combination (m.13708*A + PVT1 rs4410871*T). The existence of epistatic biallelic combination can reflect the genuine mitonuclear epistasis.


Assuntos
Núcleo Celular/genética , DNA Mitocondrial/genética , Predisposição Genética para Doença/genética , Genoma Mitocondrial/genética , Esclerose Múltipla/genética , Adulto , Antígenos CD/genética , Antígenos de Diferenciação de Linfócitos T/genética , Antígeno B7-2/genética , Feminino , Estudos de Associação Genética , Humanos , Subunidade alfa de Receptor de Interleucina-7/genética , Lectinas Tipo C/genética , Masculino , Mitocôndrias/genética , Proteínas de Transporte de Monossacarídeos/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética
20.
PLoS One ; 15(7): e0235430, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722672

RESUMO

Phylogeographic relationships among global collections of the mosquito Aedes aegypti were evaluated using the mitochondrial Cytochrome C Oxidase 1 (CO1) and NADH dehydrogenase subunit 4 (ND4) genes including new sequences from Sri Lanka. Phylogeographic analysis estimated that Ae. aegypti arose as a species ~614 thousand years ago (kya) in the late Pleistocene. At 545 kya an "early" East African clade arose that continued to differentiate in East Africa, and eventually gave rise to three lineages one of which is distributed throughout all tropical and subtropical regions, a second that contains Southeast Asian/Sri Lankan mosquitoes and a third that contains mostly New World mosquitoes. West African collections were not represented in this early clade. The late clade continued to differentiate throughout Africa and gave rise to a lineage that spread globally. The most recent branches of the late clade are represented by South-East Asia and India/Pakistan collections. Analysis of migration rates suggests abundant gene flow between India/Pakistan and the rest of the world with the exception of Africa.


Assuntos
Aedes/genética , DNA Mitocondrial/genética , Mitocôndrias/genética , Filogeografia , Aedes/classificação , África , África Oriental , Animais , Complexo IV da Cadeia de Transporte de Elétrons/genética , Fluxo Gênico , Genes Mitocondriais/genética , Haplótipos , Índia , Mitocôndrias/metabolismo , Paquistão , Filogenia , Sri Lanka
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