mtDNA Polymorphisms Research Articles

Forensic efficiency evaluation of a mtDNA whole genome sequencing system constructed with long fragment amplification strategy on DNA nanoball sequencing platform

Mitochondrial DNA (mtDNA) is an important genetic marker for degraded biological sample identification, maternal pedigree tracing, and population genetic structure study owing to its characteristics of high copy number, anti-degradable ring structure, and maternal inheritance. Whole mtDNA genome sequencing is an optimal method for the analysis of mtDNA polymorphism and heterogeneity because it allows for the comprehensive use of maternal genetic information. However, because of lacking quantitative evaluations for sequencing data, the scientific interpretation standards for mtDNA sequencing results of the previously used sequencing systems are often different, and false positive or false negative results are prone to occur when faced with the interference of nuclear genomic DNA, or the heterogeneities of mtDNA sequence and structure. In this study, we evaluated a novel mtDNA whole genome sequencing system using long fragment amplification strategy on the DNA nanoball (DNB) sequencing platform. This system demonstrated high sequencing quality and specific mtDNA sequencing efficiencies on positive control DNA and FTA bloodstain samples, as the average Q20 and Q30 values of the corresponding samples were 97.17 % and 91.93 %; 97.37 % and 92.48 %, respectively. The mean mapping percentages for the reference sequences of whole genome DNA (wgDNA), mtDNA, and nuclear genomic DNA (ngDNA) in the corresponding samples were 99.98 %, 99.97 %, 0.03 %, and 99.91 %, 99.40 %, 0.60 %; respectively. The average error calling rates for the bases A, C, G, and T of the whole mtDNA genome were 0.2519 %, 0.2550 %, 0.2906 %; and 0.2392 %, respectively. The efficacy of heteroplasmy identification was assessed using a set of theoretical sites with predetermined rates. These sites were created by combining the samples with known mtDNA haplotypes in certain proportions. The absolute errors between observed and theoretical heteroplasmy values were 89.59 %, 74.68 %, 50.20 %, 12.65 %, 8.31 %, and 4.85 %, while the theoretical heteroplasmy values were 5 %, 10 %, 20 %, 80 %, 90 %, and 95 %, respectively. The absolute error exhibited relative stability when the mtDNA sequencing depth exceeded 500×. Furthermore, the system sequencing efficiency was also confirmed among different kinds of samples, and these samples included natural samples (e.g., peripheral blood samples preserved on FTA cards for 2 and 11 years, and on filter paper for 6 and 9 years), degraded samples, sensitivity samples, samples derived from various bodily fluids, and maternal pedigree samples. In summary, the whole mtDNA genome sequencing system used for forensic identification demonstrated high performance in analyzing mtDNA sequence information, and showed significant prospects for forensic application and maternal genetic research.

Retracted: MtDNA polymorphism analyses in the Chinese Mongolian group: Efficiency evaluation and further matrilineal genetic structure exploration.

Qiong Lan, Tong Xie, Xiaoye Jin, Yating Fang, Shuyan Mei, Guang Yang, Bofeng Zhu. MtDNA polymorphism analyses in the Chinese Mongolian group: Efficiency evaluation and further matrilineal genetic structure exploration. Molec Genet Genom Med 7:e934, 2019 (https://doi.org/10.1002/mgg3.934). The above article, published online on 3 September 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Suzanne Hart, and Wiley Periodicals LLC. Following publication of this article, concerns were raised by a third party regarding consent and ethical approval for the research undertaken and reported in the article. The publisher and representatives of the journal's editorial board undertook a review of the consent documentation provided, against the research performed and reported in the article. The review uncovered inconsistencies between the consent documentation and the research reported; the documentation was not sufficiently detailed to resolve the concerns raised. As a result, the parties have made the decision to retract the article. In addition, consent documentation did not give approval for data associated with this article to be shared publicly. The associated data for this article has been withdrawn from the publication record following a concern that the data could be used to identify those who have participated in the research. Qiong Lan, Xiaoye Jin, and Bofeng Zhu responded on behalf of all the authors, who disagree with the retraction.

Commercial suitability and characterization of newly developed Erucastrum canariense (Can) sterile cytoplasm based cytoplasmic male sterile (CMS) lines in Indian cauliflower

The study presents the first to characterize novel Erucastrum canarianse Webb and Berthel (or Can) sterile cytoplasm-based CMS lines in Indian cauliflower (Brassica oleracea var. botrytis L.) and investigating their commercial suitability. Eleven Can-based CMS lines were examined for 12 agro-morphological and yield traits,18 floral traits, four seed yield traits together with three each of the Ogura (source: wild Japanese Radish) and Tour (Source: Brassica tournefortii) cytoplasms. All of the recorded floral and seed traits showed significant (P > 0.05) differences between the CMS lines of each group. Agro-morphological and yield traits in CMS lines and their maintainers, however, were non-significantly different. All the Can- and Ogura-based CMS lines showed flowering and appropriate seed formation by natural cross-pollination. Only two Tour cytoplasm-based CMS lines, Tour (DC-41-5) and Tour (DC-67), produced the smallest malformed flowers and stigma. The highest seed yield per plant in CMS lines was in Ogu (DC-98-4) and the lowest in Tour (DC-67). P14 and P15, two polymorphic mtDNA markers, were discovered for the Can CMS system for early detection. Five primers (ITS5a-ITS4, atpF-atpH, P16, rbeL and trnL), along with their maintainers, were sequenced and aligned to detect nucleotide changes including as additions and or deletions at different positions. The newly introduced E. canariense sterile cytoplasm-based CMS system in cauliflower is the subject of the first comprehensive report, which emphasises their potential as a further stable and reliable genetic mechanism for hybrid breeding.

Functional ability of mitochondria and mitochondrial genome polymorphism as factors affecting arrhythmogenesis in chronic coronary artery disease

Aim. To investigate functional state of mitochondria and mitochondrial DNA (mtDNA) polymorphism in coronary artery disease (CAD) patients with life-threatening cardiac rhythm disorders (CRD).Methods. We investigated venous blood samples of 45 patients with uncomplicated CAD and 120 CAD patients with CRD. Oxygen consumption rate of mitochondrias of leukocytes in V3 and V4 states were determined in pyruvate-malate and succinate buffers, as well as in the presence of palmitic acid (PA). In patients with complicated CAD, mtDNA haplogroup and substitutions in gene encoding proteins of the respiratory chain complexes and mitochondrial rRNA were determined. Statistical analysis was performed using Mann-Whitney, Wilcoxon tests and Chi-square test with Yates’ correction.Results. In CAD and CAD with CRD, oxygen consumption rate of intact mitochondria did not different in either pyruvate-malate or succinate buffers. In uncomplicated CAD, PA supplementation increases oxygen consumption rate by mitochondria in both succinate and pyruvate-malate buffers. The majority of patients (41%) with CAD and CRD were carriers of the haplogroup «H» and, in this indicator, the sample did not differ from patients with uncomplicated CAD. However, mtDNA of patients with complicated CAD was characterized by a more frequent combined carriage of two and more missense substitutions in genes of respiratory chain and rRNA.Conclusion. Mitochondria of patients with coronary artery disease and life-threatening cardiac rhythm disorders have reduced functional reserve. The distribution of frequencies of main mtDNA haplogroups of patients with coronary artery disease with life threatening cardiac rhythm disorders corresponds to the population. The mtDNA of such patients is characterized by a high frequency of carriage of combined polymorphisms in gene of electron transport chain proteins and rRNA.

Assessment of body fluid identification and DNA profiling after exposure to tropical weather conditions.

Despite current advances in body fluid identification, there are few studies evaluating the effect of environmental conditions. The present work assessed the detection of body fluids, blood, semen, and saliva, through lateral flow immunochromatographic (LFI) tests, exposed to tropical weather conditions over time, also evaluating the possibility of obtaining STR (short tandem repeat) profiles and identifying mitochondrial DNA (mtDNA) polymorphisms. Blood, semen, saliva samples, and mixtures of these fluids were deposited on polyester clothes and exposed to open-air tropical weather conditions for 1 month. The test versions from LFI (SERATEC®, Germany) Lab and crime scene (CS) used for the detection - one per each body fluid type - demonstrated that it is possible to identify body fluids and their mixtures up to 14 days after deposition. At 30 days, blood and semen were detected but not saliva. Full STR profiles were obtained from 14-day-old blood samples, and partial profiles were obtained from the remaining samples. It was possible to sequence mtDNA in the samples previously analyzed for STR profiling, and haplogroups could be assigned. In conclusion, this study demonstrated for the first time the possibility of body fluid identification and DNA profiling after exposure to tropical weather conditions for 1 month and also demonstrated the value of mtDNA analysis for compromised biological evidence.

Association analysis of mitochondrial genome polymorphisms with backfat thickness in pigs

Mitochondrial DNA (mtDNA) variations and associated effects on economic traits have been widely reported in farm animals, as these genetic polymorphisms can affect the efficiency of energy production and cell metabolism. In studies related to metabolism, the deposition of fat was highly correlated with mitochondria. However, the effect of mtDNA polymorphisms on porcine backfat thickness (BFT) remained unclear. In this study, 243 pigs were collected to analyse the relationship between BFT and mtDNA polymorphisms. There were considerable differences in BFT, ranging from 5 mm to 18 mm. MtDNA D-loop sequencing discovered 48 polymorphic sites. Association analysis revealed that 30 variations were associated with BFT (P < 0.05). The polymorphism m.794A > G showed the maximum difference in BFT between A and G carriers, which differed at ∼2.5 mm (P < 0.001). The 48 polymorphic sites generated 22 haplotypes (H1-H22), which clustered into 4 haplogroups (HG1-HG4). HG1 had a lower BFT value than other three haplogroups (P < 0.01), whereas H4 in HG1 exhibited the lowest BFT of all haplotypes analyzed (P < 0.01). The results of this study highlight an association between mtDNA polymorphisms and BFT, and suggest the potential application of mtDNA in pig molecular breeding practices.

Mitochondrial heteroplasmy as a marker for premature coronary artery disease: analysis of the poly-C tract of the control region sequence

Abstract Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern, being more prone to acquire somatic novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production, involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs 21.21%, p&amp;lt;0.01) and dyslipidemia (38.83% vs 28.41%, p=0.02) were significant more frequent among STEMI patients. Besides, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI cases than in controls. The OR associated C16223T mtDNA mutation with an increased presence of cardiovascular risk factors. Our data suggest that mtDNA C16223T mutation and poly-C heteroplasmy may be associated with unstable atherosclerosis disease. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated to C16223T mtDNA mutation, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Thus, preventing exposure to the damaging mechanisms associated to CVRFs is of the utmost importancemtDNA sanger analysisBaseline characteristics.

Single nucleotide polymorphism rs527236194 of the cytochrome B gene (MT-CYB) is associated with alterations in sperm parameters.

The mitochondrial genome is substantially susceptible to mutations and has high polymorphism due to structural features, location, and lack of recombinant variability, as its inheritance is strictly maternal. All of these events can be accompanied by the accumulation of mitochondrial single nucleotide polymorphisms (mtSNPs) in the sperm. The aim of this research was to analyze the influence of mutations in the MT-CYB gene on sperm quality. We conducted a case‒control study to identify mutations in the mitochondrial cytochrome B (MT-CYB) gene in men with asthenoteratozoospermia (89 cases) and oligoasthenoteratozoospermia (65 cases). The comparison group consisted of 164 fertile men. Somatic cell lysis followed by mtDNA extraction was conducted to analyze three mtDNA polymorphisms, rs28357373 (T15629C (Leu295=), rs527236194 (T15784C (p.Pro346=), rs2853506 (A15218G, p.Thr158Ala). Detection and genotyping of polymorphic loci in the MT-CYB gene was performed using the TaqMan allelic discrimination assay. To verify mutations in the MT-CYB gene, automated Sanger DNA sequencing was used. We found that rs527236194 was associated with asthenoteratozoospermia. rs28357373 in the MT-CYB gene did not show any polymorphism in the analyzed groups, which indicates a rare frequency of the TT genotype in our region. Rs28357373 and rs2853506 are not associated with male sperm abnormalities in the Volga-Ural region. The association of the rs527236194 polymorphic variant with sperm parameter alterations suggests its role in the pathophysiology of male infertility and requires further investigation in larger samples.

Influence of the Rate of Changes in the COX1 Gene on Body Size and Sexual Selection in Carp Hybridization

The influence of mtDNA cytochrome c-oxidase I gene fragment variability on body length was studied in twelve species of cyprinids, which may have hybrids with Rutilus rutilus L. and Abramis brama L., and in reciprocal hybrids (RA, AR) and alloplasmatic backcrosses (ARR, RAA) of roach (R) and bream (A). It has been established that the rate of nucleotide substitutions in COX1 is negatively related not only to body size but also to fish life span, which differentiates them into two groups: group I – species with a high rate of COX1 changes and a relatively small body size and group II – species with low sequence variability and relatively large body size. The boundary for the distinguished groups runs between species the same genus Leuciscus leuciscus and L. idus: with a twofold decrease in the rate of substitutions in ide, a twofold increase in body size and lifespan occurs, which indicates a decrease in the rate of cellular respiration and free radical leak, and the exact mitonuclear match respiratory complexes. Presumably, the decrease in the rate of COX1 changes in species of group II and in bleak Alburnus alburnus is associated with an increase in the size of genome, which provides additional protection of genes from chemical mutagens and, regardless of body size, reduces the rate of aerobic metabolism. It has been experimentally shown that mtDNA affects body length. When bream mtDNA is included in the roach nuclear genome, ARR backcrosses have the body length of a bream and high viability, while RAA backcrosses with roach mtDNA and the bream nuclear genome inherit the roach body length and reduce viability. Species of group II are not able to effectively use the highly polymorphic mtDNA of species of group I, which is also manifested by a violation of the inheritance of a longer bream body length in RA hybrids and leads to reproductive isolation. Group I species, such as Rutilus rutilus, can include mtDNA of both groups in their genome, which underlies sexual selection in hybridization. Accordingly, sexual size dimorphism has a genetic origin, and body size for a potential partner can be a signal for determining the mitonuclear compatibility of genomes in respiratory complexes.

MtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.

Genetic Diversity of the Eastern Subspecies of Red Deer (Cervus elaphus) in Russia Revealed by mtDNA and Microsatellite Polymorphism

Genetic Diversity of the Eastern Subspecies of Red Deer (Cervus elaphus) in Russia Revealed by mtDNA and Microsatellite Polymorphism

Phylogenetic Analysis of Russian Native Sheep Breeds Based on mtDNA Sequences.

Eurasia is represented by all climatic zones and various environments. A unique breed variety of farm animals has been developed in Russia, whose territory covers a large area of the continent. A total of 69 local breeds and types of dairy, wool, and meat sheep (Ovis aries) are maintained here. However, the genetic diversity and maternal origin of these local breeds have not been comprehensively investigated. In this study, we describe the diversity and phylogeny of Russian sheep breeds inhabiting different geographical regions based on the analysis of complete sequences of mitochondrial genomes (mtDNA). Complete mtDNA sequences of the studied sheep were obtained using next-generation sequencing technology (NGS). All investigated geographical groups of sheep were characterized by high haplotype (Hd = 0.9992) and nucleotide diversity (π = 0.00378). Analysis of the AMOVA results showed that genetic diversity was majorly determined by within-population differences (77.87%). We identified 128 haplotypes in all studied sheep. Haplotypes belonged to the following haplogroups: B (64.8%), A (28.9%), C (5.5%), and D (0.8%). Haplogroup B was predominant in the western part of Russia. A high level of mtDNA polymorphism in the studied groups of local sheep indicates the presence of a significant reserve of unique genotypes in Russia, which is to be explored.

CmVCall: An automated and adjustable nanopore analysis pipeline for heteroplasmy detection of the control region in human mitochondrial genome

Genetic associations between human mitochondrial DNA (mtDNA) heteroplasmy and mitochondrial diseases, aging, and cancer have been elaborated, contributing a lot to the further understanding of mtDNA polymorphic spectrum in anthropology, population, and forensic genetics. In the past decade, heteroplasmy detection using Sanger sequencing and next generation sequencing (NGS) was hampered by the former’s inefficiency and the latter’s inherent bias due to amplification and mapping of short reads, respectively. Nanopore sequencing stands out for its ability to yield long contiguous segments of DNA, providing a new insight into heterogeneity authentication. In addition to MinION from Oxford Nanopore Technologies, an alternative nanopore sequencer QNome (Qitan Technology) has also been applied to various biological research and the forensic applicability of this platform has been proved recently. In this study, we evaluated the performance of four commonly used variant callers in the heterogeneity authentication of the control region of human mtDNA based on simulations of different ratios generated by mixing QNome nanopore sequencing reads of two synthetic sequences. Then, an open-source and python-based nanopore analytics pipeline, CmVCall was developed and incorporated multiple programs including reads filtering, removal of nuclear mitochondrial sequences (NUMTs), alignment, optional ‘Correction’ mode, and heterogeneity identification. CmVCall can achieve high precision, accuracy, and recall of 100%, 99.9%, and 92.3% with a 5% heteroplasmy level in ‘Correction’ mode. Moreover, blood, saliva, and hair shaft samples from monozygotic (MZ) twins were used for heterogeneity evaluation and comparison with the NGS data. Results of MZ twin samples showed that CmVCall could identify more point heteroplasmy sites, revealing significant levels of inter- and intra-individual mtDNA polymorphism. In conclusion, we believe that this analysis pipeline will lay a solid foundation for the development of a comprehensive nanopore analysis pipeline targeting the whole mitochondrial genome.

Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-β among women with polycystic ovary syndrome: a cross-sectional study.

Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility in women of childbearing age, and many patients with PCOS have obesity and insulin resistance (IR). Although obesity is related to an increased risk of IR, in clinical practice, PCOS patients exhibit different effects on improving insulin sensitivity after weight loss. Therefore, in the present study, we aimed to examine the moderating effect of polymorphisms of mtDNA in the D-loop region on the associations of body mass index (BMI) with the homeostasis model assessment of insulin resistance index (HOMA-IR) and pancreatic β cell function index (HOMA-β) among women with PCOS. Based on a cross-sectional study, women with PCOS were recruited from the Reproductive Center of the First Affiliated Hospital of Anhui Medical University from 2015 to 2018. A total of 520 women who were diagnosed with PCOS based on the revised 2003 Rotterdam criteria were included in the study. Peripheral blood was collected from these patients, followed by DNA extraction, PCR amplification, and sequencing at baseline. HOMA-IR and HOMA-β were calculated according to blood glucose-related indices. Moderating effect models were performed with BMI as an independent variable, polymorphisms of mtDNA in the D-loop region as moderators, and ln (HOMA-IR) and ln (HOMA-β) as dependent variables. To verify the stability of moderating effect, sensitivity analysis was performed withthe quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose/fasting insulin (G/I), and fasting insulin as dependent variables. BMI was positively associated with ln (HOMA-IR) and ln (HOMA-β) (β = 0.090, p < 0.001; β = 0.059, p < 0.001, respectively), and the relationship between BMI and ln (HOMA-IR) or ln (HOMA-β) was moderated by the polymorphisms of mtDNA in the D-loop region. Compared with the respective wild-type, the variant -type of m.16217 T > C enhanced the association between BMI and HOMA-IR, while the variant-type of m.16316 A > G weakened the association. On the other hand, the variant-type of m.16316 A > G and m.16203 A > G weakened the association between BMI and HOMA-β, respectively. The results of QUICKI and fasting insulin as dependent variables were generally consistent with HOMA-IR, and the results of G/I as dependent variables were generally consistent with HOMA-β. Polymorphisms of mtDNA in the D-loop region moderate the associations of BMI with HOMA-IR and HOMA-β among women with PCOS.

Biodiversity of pigs of various breeds based on the analysis of mtDNA D-loop

Mitochondrial DNA polymorphism, which is one of the most common genetic markers, is actively used in the study of various animal species. Since the mitochondrial genome has evolved over many years within a species, this has influenced the fixation of mutations and the formation of mitochondrial lineages that share a common origin and form mitochondrial genomes, called mtDNA haplogroups. The objectives of the work were to evaluate the genetic diversity of pigs of two maternal breeds of domestic reproduction based on the analysis of mtDNA D-loop polymorphism and to compare the results obtained with identical sequences from the NCBI database by breed and their geographic distribution. 39 Landrace pigs and 49 Large White pigs were used for the study. MtDNA was isolated from tissue samples (ear notch). The number of haplotypes, haplotypic and nucleotide diversity, and the average number of nucleotide substitutions per site were determined to assess the genetic diversity. 23 polymorphic sites were found: 21 in Landrace pigs, 17 in Large White pigs. A total of ten haplotypes were identified in the study population. The NCBI database found 75 identical sequences for pigs of different breeds bred around the world. After determining the nucleotide sequences of the D-loop fragment of the mtDNA of Landrace and Large White pigs of domestic reproduction and comparing them with the sequences from the NCBI database, the presence of identical sequences in the animals we studied and in the representatives of European and Asian breeds, including commercial and local was established. The materials obtained show that the assessment of mtDNA polymorphism contributes to the identification of phylogenetic relationships between populations, tracing of pedigree processes, and can be considered as an additional criterion of selection and breeding work.

Human Mitochondrial DNA Haplogroup M5 is Associated with Type 2 Diabetes Mellitus in South Indian Population: A High-Resolution Case Control Study‌ using Next Generation Sequencing

Energy is required for life on Earth, and it is provided by the small organelles of cells called mitochondria, also referred to as the cell's powerhouses. Mitochondrial DNA (mtDNA), which is grouped into several human mtDNA haplogroups, is frequently employed in population genetics to identify individuals or communities based on mutation sites found by comparison with the reference sequence (rCRS). Previous studies in various populations have connected particular mtDNA haplogroups and polymorphisms to a range of human disorders, including Type 2 Diabetes Mellitus (T2DM). In addition, a number of mitochondrial DNA polymorphisms have been connected to elevated reactive oxygen species (ROS) generation and an elevated risk of a number of malignancies, including type 2 diabetes mellitus (T2DM), in the Indian patients. As a result, we conducted a high-resolution assessment of the mtDNA hypervariable area in our study to trace distinct mtDNA haplogroup connections with type 2 Diabetes Mellitus (T2DM) in south Indian communities. We discovered that mtDNA Haplogroup M was present in 60% of type 2 Diabetes Mellitus (T2DM) patients and about 55% of the control samples examined. Haplogroup M is the most frequent mtDNA cluster observed in south Indian people. We further segmented macro haplogroup M and revealed sub haplogroups (M8, M7, M6, M5, M3, and M2) with variable frequencies. Patients with Type 2 Diabetes Mellitus (T2DM) and haplogroup M5 were significantly associated, according to our research (p = 0.026). Haplogroup M5 was discovered in our study in 3.3 percent of control populations and 13% of south Indian T2DM patients. These results imply that Type 2 Diabetes Mellitus is more likely to occur in haplogroup M5 individuals.

Mitochondrial Heteroplasmy as a Marker for Premature Coronary Artery Disease: Analysis of the Poly-C Tract of the Control Region Sequence

Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production and involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs. 21.21%, p < 0.01) and dyslipidemia (38.83% vs. 28.41%, p = 0.02) were significantly more frequent among STEMI patients. Moreover, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI male patients than in controls. The OR associated C16223T mtDNA with the increased presence of cardiovascular risk factors. Our data suggest that mtDNA 16223T and heteroplasmy may be associated with unstable premature atherosclerosis disease in men. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated with C16223T mtDNA, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Preventing exposure to the damaging mechanisms associated with CVRFs is of utmost importance.

Mitochondrial DNA Polymorphism in HV1 and HV2 Regions and 12S rDNA in Perimenopausal Hypertensive Women.

Estrogens enhance cellular mitochondrial activity. The diminution of female hormones during menopause may have an effect on the mitochondrial genome and the expression of mitochondrial proteins. Hence, oxidative stress and the pro-inflammatory state contribute to the formation of systemic illnesses including arterial hypertension (AH). This study aimed to determine the types and frequency of mutations in the mitochondrial DNA (mtDNA) nucleotide sequence in the hypervariable regions 1 and 2 (HV1 and HV2) and the 12S RNA coding sequence of the D-loop in postmenopausal women with hypertension. In our study, 100 women were investigated, 53 of whom were postmenopausal and 47 of whom were premenopausal (53.9 ± 3.7 years vs. 47.7 ± 4.2 years, respectively). Of those studied, 35 premenopausal and 40 postmenopausal women were diagnosed with AH. A medical checkup with 24 h monitoring of blood pressure (RR) and heart rate was undertaken (HR). The polymorphism of the D-loop and 12S rDNA region of mtDNA was examined. Changes in the nucleotide sequence of mtDNA were observed in 23% of the group of 100 women. The changes were identified in 91.3% of HV1 and HV2 regions, 60.9% of HV1 segments, 47.5% of HV2 regions, and 43.5% of 12S rDNA regions. The frequency of nucleotide sequence alterations in mtDNA was substantially higher in postmenopausal women (34%) than in premenopausal women (10.6%), p = 0.016. A higher frequency of changes in HV1 + HV2 sections in postmenopausal women (30.2%) compared to the premenopausal group (10.6%) was detected, p = 0.011. Only postmenopausal women were found to have modifications to the HV2 segment and the 12S rDNA region. After menopause, polymorphism in the mtDNA region was substantially more frequent in women with arterial hypertension than before menopause (p = 0.030; 37.5% vs. 11.5%). Comparable findings were observed in the HV2 and HV1 regions of the AH group (35% vs. 11.5%), p = 0.015, in the HV1 segment (25% vs. 11.5%), p = 0.529, and in the HV2 segment, 12S rDNA (25% vs. 0%). More than 80% of all changes in nucleotide sequence were homoplasmic. The mtDNA polymorphisms of the nucleotide sequence in the HV1 and HV2 regions, the HV2 region alone, and the 12S RNA coding sequence were associated with estrogen deficiency and a more severe course of arterial hypertension, accompanied by symptoms of adrenergic stimulation.

Diversity of Wolbachia infection and its influence on mitochondrial DNA variation in the diamondback moth, Plutella xylostella

Plutella xylostella is a pest that severely damages cruciferous vegetables worldwide and has been shown to be infected with the maternally inherited bacteria Wolbachia, with the main infected strain was plutWB1. In this study, we performed a large-scale global sampling of P. xylostella and amplified 3 mtDNA genes of P. xylostella and 6 Wolbachia genes to analyze the infection status, diversity of Wolbachia in P. xylostella, and its effect on mtDNA variation in P. xylostella. This study provides a conservative estimate of Wolbachia infection rates in P. xylostella, which was found to be 7% (104/1440). The ST 108 (plutWB1) was shared among butterfly species and the moth species P. xylostella, revealing that Wolbachia strain plutWB1 acquisition in P. xylostella may be through horizontal transmission. The Parafit analyses indicated a significant association between Wolbachia and Wolbachia-infected P. xylostella individuals, and individuals infected with plutWB1 tended to cluster in the basal positions of the phylogenetic tree based on the mtDNA data. Additionally, Wolbachia infections were associated with increased mtDNA polymorphism in the infected P. xylostella population. These data suggest that Wolbachia endosymbionts may have a potential effect on mtDNA variation of P. xylostella.

Polymorphism of mitochondrial DNA genes involved in asthenozoospermia in infertile patients of Côte d’Ivoire

Objective: The relationship between mitochondrial DNA (mtDNA) polymorphisms and abnormalities in sperm quality has been the subject of several studies, with the objective of improving the treatment of male infertility. This study, which contributes to the identification of genetic markers of sperm abnormalities, was conducted to study mtDNA mutations in the asthenozoospermia profile. Methods: This case-control study included 30 patients with asthenozoospermia and 28 with normospermia after spermogram and spermocytogram analyses. After the extraction of total DNA from the spermatozoa of 58 ejaculates from these individuals using the phenol-chloroform method, the amplification of genes of interest in mtDNA using specific primers was performed by conventional polymerase chain reaction, and sequencing was used to detect mutations. Results: Male patients with asthenozoospermia in the tertiary sector had significantly more mutant- than wild-type (P = 0.0005) MT-CO II genes. Similarly, for the same gene, males with asthenozoospermia and primary infertility had significantly more mutants than the wild-type (P = 0.001). Sequencing revealed 29 mutations that were observed only with asthenozoospermia, which could be the basis for low sperm mobility. Conclusion: This study identified several mutations in mtDNA genes that could be considered genetic markers of asthenozoospermia if confirmed in a deeper study.