Mitochondrial DNA Polymorphisms Research Articles

Lack of association between mitochondrial DNA polymorphisms and didexoxynucleoside-induced hyperlactataemia in black-African, HIV-1-infected patients

Background: Recent studies have shown some association between specific mitochondrial DNA (mtDNA) polymorphisms and peripheral neuropathy in both white European and black American populations. An association between mtDNA haplogroup H and peripheral lipoatrophy has been reported in white Europeans. Our group has shown a lack of association between mtDNA polymorphisms and the occurrence of HL in white Europeans exposed to dideoxynucleosides, but there have been no studies in black African people. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P96 Cite this article as: Arenas-Pinto et al.: Lack of association between mitochondrial DNA polymorphisms and didexoxynucleoside-induced hyperlactataemia in black-African, HIV-1-infected patients. Journal of the International AIDS Society 2010 13(Suppl 4):P96. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113104/

Mitochondrial DNA and TFAM gene variation in early-onset myocardial infarction: Evidence for an association to haplogroup H

The main objective of this research was to define the association between common mitochondrial DNA (mtDNA) polymorphisms and mitochondrial transcription A gene ( TFAM) variants and myocardial infarction (MI) in patients with atherosclerotic diseased vessels. Ten mitochondrial polymorphisms that defined the nine common European haplogroups were genotyped in 500 male patients with early onset MI (< 55 years) and at least one atherosclerotic coronary vessel (angiographically confirmed), and 500 healthy controls. In addition, we searched for DNA variants in the coding region of the TFAM gene and compared patients and controls for the allele and genotype frequencies. Early onset MI was strongly associated with male gender and tobacco smoking in our population. MtDNA haplogroup H (defined by allele 7028 °C) was significantly more frequent in a first group of patients ( n = 250) compared to controls ( n = 300), and the association was confirmed in a second group of only smokers (250 patients and 200 controls). For total patients and controls, we obtained a p = 0.002 (OR = 1.50; 95% CI = 1.17–1.92) for H vs. the other haplogroups. We found four common TFAM polymorphisms, with allele/genotype frequencies that did not differ between patients and controls. In conclusion, mitochondrial haplogroup H was associated with early onset MI in male smokers. Our work supported a role for the mtDNA variation in the risk for atherosclerosis and ischemic associated events, likely due to differences in mitochondrial function and reactive oxygen production between the different haplogroups.

Control of inoculated fermentations in wine cellars by mitochondrial DNA analysis of starter yeast

The main purpose of this work was to test the effective dominance of the inoculated strain during the fermentation process. During this research activity, two Saccharomyces cerevisiae selected strains, isolated from Aglianico del Vulture grapes, were tested during inoculated fermentations at pilot scale in three wine cellars producing Aglianico del Vulture wine and characterized by different typologies. Yeast colonies sampled during the processes of fermentation were identified by restriction analysis of the internal transcribed spacer (ITS) region, and S. cerevisiae strains were differentiated by restriction fragment length polymorphism of mitochondrial DNA (RFLP-mtDNA). Analysis of the yeast population during the inoculated fermentations evidenced a significant presence of non-Saccharomyces, which varied with the cellar. The presence of non-Saccharomyces yeasts at different levels affected the aromatic composition of the experimental wines, as determined by gas-chromatographic analysis. The RFLP-mtDNA of S. cerevisiae isolates revealed the differing dominance of inoculated strains as a function of the wine cellar. In two cellars, all the isolates showed the same restriction profile, which was identical to that of the starter pattern. In contrast, in the third cellar, a significant percentage of S. cerevisiae isolates exhibited mtDNA-RFLP patterns different from the yeast starter profile, showing that, in this case, the starter exhibited low dominance in the fermentation. Our results demonstrate that, although the inoculated strains were found with high frequency, other yeasts (S. cerevisiae and non-Saccharomyces) developed, contributing to the fermentative process and to organoleptic quality of the final wine.

Mitochondrial haplogroups associated with elite Japanese athlete status

PurposeIt has been hypothesised that certain mitochondrial haplogroups, which are defined by the presence of a characteristic cluster of tightly linked mitochondrial DNA polymorphisms, would be associated with elite Japanese...

Mitochondrial DNA polymorphisms in Gelao ethnic group residing in Southwest China

Gelao ethnic group, an aboriginal population residing in southwest China, has undergone a long and complex evolutionary process. To investigate the genetic structure of this ancient ethnic group, mitochondrial DNA (mtDNA) polymorphisms of 102 Gelao individuals were collected and analyzed in this study. With the aid of the information extracted from control-region hypervariable segments (HVSs) I and II as well as some necessary coding-region segments, phylogenetic status of all mtDNAs under study were determined by means of classifying into various defined haplogroups. The southern-prevalent haplogroups B, R9, and M7 account for 45.1% of the gene pool, whereas northern-prevalent haplogroups A, D, G, N9, and M8 consist of 39.2%. Haplogroup distribution indicates that the Gelao bears signatures of southern populations and possesses some regional characters. In the PC map, Gelao clusters together with populations with Bai-Yue tribe origin as well as the local Han and the Miao. The results demonstrate the complexity of Gelao population and the data can well supplement the China mtDNA database.

Identification of genetic polymorphisms in bovine mitochondrial deoxyribonucleic acid1

In this study, the intent was to identify genetic polymorphisms of mitochondrial (mt) DNA in Korean cattle (Bos taurus coreana) and to analyze the genetic relationship between Korean cattle and other breeds. Whole mtDNA genomes (16,338 bp) of 26 animals (16 Korean cattle and 10 Holsteins) were directly sequenced. Multiple alignments, including 26 whole-mtDNA sequences obtained by direct sequencing and 10 mtDNA sequences from a public database (National Center for Biotechnology Information), revealed 393 mtDNA polymorphisms (382 SNP, 3 heteroplasmies, and 8 insertion-deletion polymorphisms). Estimated gene diversity of mtDNA was 0.00198 among these 36 animals. Phylogenic analysis with mtDNA polymorphisms revealed a distinct genetic difference between Bos taurus (Korean, Japanese Black, Holstein, and Fleckvieh breeds) and Bos indicus (Nellore and Zwergzebu breeds). The genetic information regarding mtDNA polymorphisms identified in this study would be useful for further investigation of mtDNA in other breeds.

The 5178C/A and 16189T/C polymorphisms of mitochondrial DNA in Korean men and their associations with blood iron metabolism

Several studies reported that there were the associations between the genetic polymorphisms in the mitochondrial DNA (mtDNA) and some blood iron markers. Thus, we tried to investigate the relationship between two genetic polymorphisms (5178C/A and 16189T/C) in the mtDNA and several blood iron markers in Korean men. A total of unrelated 131 Korean men were participated in this study. Two genetic polymorphisms in the mtDNA was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method, and hematological or biochemical assay performed by autoanalyzer. Although the 16189T/C polymorphism was not significantly associated with any iron parameters measured in this study, we found that the 5178C/A polymorphism was significantly associated with red blood cell (RBC) count and hematocrit (HCT) value in Korean men (P < 0.05). Therefore, our data suggest that the 5178C/A polymorphism in the mtDNA might be useful as a genetic marker with respect to blood iron metabolism.

TTR familial amyloid polyneuropathy: does a mitochondrial polymorphism entirely explain the parent-of-origin difference in penetrance?

The Val30Met transthyretin familial amyloid polyneuropathy (TTR-V30M-FAP) is the most frequent familial amyloidosis, with autosomal dominant transmission. This severe disease shows important differences in age of onset and penetrance. Recently, a difference in penetrance according to the gender of the transmitting parent was elicited in different geographic areas with a higher penetrance in case of maternal transmission of the trait. In addition, differences in mitochondrial haplogroup distribution in early and late onset Swedish and French cases of TTR-V30M-FAP suggested that a polymorphism of mitochondrial DNA could be one underlying mechanism of the phenotypic variation. We further investigated this hypothesis by modeling the penetrance function with a parent-of-origin and/or a mitochondrial polymorphism effect in samples of Portuguese (n=33) and Swedish families (n=86) with TTR-V30M-FAP in which several individuals had been tested for mitochondrial haplogroups. Our analysis showed that a mitochondrial polymorphism effect was sufficient to explain the observed difference in penetrance according to gender of the transmitting parent in the Portuguese sample, whereas, in the Swedish sample, a clear residual parent-of-origin effect remained. This study further supported the role of a mitochondrial polymorphism effect that might induce a higher penetrance in case of maternal inheritance of the disease. In clinical practice, these results might help to better delineate the individual disease risk and have a significant impact on the management of both patients and carriers.

Differentiation diversity of mouse parthenogenetic embryonic stem cells in chimeric mice

Recent studies have illustrated multiple differentiation potentials of embryonic stem cells (ESCs), derived from parthenogenetic embryos, to various kinds of cells (all three embryonic germ layers). However, differentiation diversity of the parthenogenetic ESCs (PgESCs) in vivo remains to be elucidated. In the present study, we established mouse PgESC-lines and observed their contribution diversity in vivo by producing chimeric mice using embryos possessing single nucleotide polymorphisms of mitochondrial DNA (mtDNA) as hosts. Based on southern blot analysis using specific probes to detect the SNPs on mtDNA, PgESC-derived mtDNA were contained in many organs such as brain, lung, and heart of the chimeric mouse. We concluded that PgESCs contributed to various internal organs in vivo, and that they were also stably maintained in adult animals.

Application of mitochondrial DNA polymorphism in the anthropology

Application of mitochondrial DNA polymorphism in the anthropology

Contrasting patterns of gene diversity between microsatellites and mitochondrial SNPs in farm and wild Atlantic salmon

Levels of genetic variability at 12 microsatellite loci and 19 single nucleotide polymorphisms in mitochondrial DNA were studied in four farm strains and four wild populations of Atlantic salmon. Within populations, the farm strains showed significantly lower allelic richness and expected heterozygosity than wild populations at the 12 microsatellite loci, but a significantly higher genetic variability with respect to observed number of haplotypes and haplotype diversity in mtDNA. Significant differences in allele- and haplotype-frequencies were observed between farm strains and wild populations, as well as between different farm strains and between different wild populations. The large genetic differentiation at mitochondrial DNA between wild populations (FST = 0.24), suggests that the farm strains attained a high mitochondrial genetic variability when created from different wild populations seven generations ago. A large proportion of this variability remains despite an expected lower effective population size for mitochondrial than nuclear DNA. This is best explained by the particular mating schemes in the breeding programmes, with 2–4 females per male. Our observations suggest that for some genetic polymorphisms farm populations might currently hold equal or higher genetic variability than wild populations, but lower overall genetic variability. In the short-term, genetic interactions between escaped farm salmon and wild salmon might increase genetic variability in wild populations, for some, but not most, genetic polymorphisms. In the long term, further losses of genetic variability in farm populations are expected for all genetic polymorphisms, and genetic variability in wild populations will be reduced if escapes of farm salmon continue.

Mitochondrial DNA Polymorphism and Phylogenetic Relationships of Proto Malays in Peninsular Malaysia

This study focus on the phylogenetic relationships among six Proto-Malay tribes (Jakun, Temuan, Semelai, Kuala, Seletar and Kanaq) and the effectiveness of using HVSI D-loop region segment and a 9bp deletion of the intergenic region of COII/tRNA of mtDNA in portraying the phylogenetic relationships. The analysis showed high pairwise differences among Kanaq, Jakun and Semelai. Thirty two haplotypes were formed from 89 D-loop sequences of Proto Malay individuals. Deletion on the 9 bp tandem repeats of COII/tRNA was detected in Semelai and Orang Kuala. Neighbor-Joining, Maximum Parsimony and Maximum Likelihood analysis revealed Jakun and Semelai haplotypes are the earliest to split from ingroups and showed that Jakun may be an ancestor for the Malay populations in the Malay Peninsular, which also support the anthropological findings. Nine basepair deletion of COII/tRNA intergenic region had occured in two clades. Results indicates a close relationships among Semelai, Temuan and Jakun. Most Kanaq and Seletar sequences were merged into tribe specific haplotypes, showing close relationships within tribes. The HVS I D-loop region of most Proto Malays are highly variable as 27 of 32 haplotypes were subgroup-specific. The HVS I of D-loop successfully revealed the close relationships among the Proto-Malays but was less effective in discriminating each tribe. Detection of ancestries for the Proto Malays using 9 bp deletion of COII/tRNA intergenic region reveals the Asian origins for Kuala and SemelAI.

Early Eurasian migration traces in the Tarim Basin revealed by mtDNA polymorphisms

The mitochondrial DNA (mtDNA) polymorphisms of 58 samples from the Daheyan village located in the central Taklamakan Desert of the Tarim Basin were determined in this study. Among the 58 samples, 29 haplotypes belonging to 18 different haplogroups were analyzed. Almost all the mtDNAs belong to a subset of either the defined Western or Eastern Eurasian pool. Extensive Eastern Eurasian lineages exist in the Daheyan population in which Northern-prevalent haplogroups present higher frequencies. In the limited existing Western Eurasian lineages, two sub-haplogroups, U3 and X2, that are rare in Central Asia were found in this study, which may be indicative of the remnants of an early immigrant population from the Near East and Caucasus regions preserved only in the Tarim Basin. The presence of U3 in modern and archeological samples in the Tarim Basin suggests that the immigration took place earlier than 2,000 years ago and points to human continuity in this area, with at least one Western lineage originating from the Near East and Caucasus regions.

Oligonucleotide indexing of DNA barcodes: identification of tuna and other scombrid species in food products.

BackgroundDNA barcodes are a global standard for species identification and have countless applications in the medical, forensic and alimentary fields, but few barcoding methods work efficiently in samples in which DNA is degraded, e.g. foods and archival specimens. This limits the choice of target regions harbouring a sufficient number of diagnostic polymorphisms. The method described here uses existing PCR and sequencing methodologies to detect mitochondrial DNA polymorphisms in complex matrices such as foods. The reported application allowed the discrimination among 17 fish species of the Scombridae family with high commercial interest such as mackerels, bonitos and tunas which are often present in processed seafood. The approach can be easily upgraded with the release of new genetic diversity information to increase the range of detected species.ResultsCocktail of primers are designed for PCR using publicly available sequences of the target sequence. They are composed of a fixed 5' region and of variable 3' cocktail portions that allow amplification of any member of a group of species of interest. The population of short amplicons is directly sequenced and indexed using primers containing a longer 5' region and the non polymorphic portion of the cocktail portion. A 226 bp region of CytB was selected as target after collection and screening of 148 online sequences; 85 SNPs were found, of which 75 were present in at least two sequences. Primers were also designed for two shorter sub-fragments that could be amplified from highly degraded samples. The test was used on 103 samples of seafood (canned tuna and scomber, tuna salad, tuna sauce) and could successfully detect the presence of different or additional species that were not identified on the labelling of canned tuna, tuna salad and sauce samples.ConclusionsThe described method is largely independent of the degree of degradation of DNA source and can thus be applied to processed seafood. Moreover, the method is highly flexible: publicly available sequence information on mitochondrial genomes are rapidly increasing for most species, facilitating the choice of target sequences and the improvement of resolution of the test. This is particularly important for discrimination of marine and aquaculture species for which genome information is still limited.

Molecular oncology focus - Is carcinogenesis a 'mitochondriopathy'?

Mitochondria are sub-cellular organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). As suggested over 70 years ago by Otto Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and in mitochondrial DNA (mtDNA) appear to be common features of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells, and some reports document the prevalence of inherited mitochondrial DNA polymorphisms in cancer patients. Nevertheless, a careful reanalysis of methodological criteria and methodology applied in those reports has shown that numerous papers can't be used as relevant sources of data for systematic review, meta-analysis, or finally for establishment of clinically applicable markers.In this review technical and conceptual errors commonly occurring in the literature are summarized. In the first place we discuss, why many of the published papers cannot be used as a valid and clinically useful sources of evidence in the biomedical and healthcare contexts. The reasons for introduction of noise in data and in consequence - bias for the interpretation of the role of mitochondrial DNA in the complex process of tumorigenesis are listed. In the second part of the text practical aspects of mtDNA research and requirements necessary to fulfill in order to use mtDNA analysis in clinics are shown. Stringent methodological criteria of a case-controlled experiment in molecular medicine are indicated. In the third part we suggest, what lessons can be learned for the future and propose guidelines for mtDNA analysis in oncology. Finally we conclude that, although several conceptual and methodological difficulties hinder the research on mitochondrial patho-physiology in cancer cells, this area of molecular medicine should be considered of high importance for future clinical practice.

258 CLASSIFICATION AND IDENTIFICATION OF THE CLONED HANWOO CALVES DERIVED FROM SOMATIC CELL NUCLEAR TRANSFER USING MS GENOTYPES AND mtDNA POLYMORPHISMS

The calves produced by somatic cell nuclear transfer (SCNT) had identical genetic background except for cytoplasmic transmission molecules, which originated from recipient oocytes. To identify the SCNT calves generated from 3 nucleus donors, genotypes for 16 microsatellite (MS) markers and mitochondrial DNA (mtDNA) polymorphisms were analyzed. Using MS genotypes, the parentage test results were not only classified as the single donor-derived calves but mtDNA sequence variations might also discriminated all SCNT calves within the donor-derived families. Comparing MS genotypes, AI-derived progenies were easily discriminated from each other. However, those genotypes could not supply the useful information for identifying the SCNT calves produced from each donor. Informative sequence variations were detected in several regions including D-loop, 12 S rDNA, and ND5 genes. About 19 nucleotide substitutions found within D-loop allowed individual identification for most SCNT-derived progeny except for 5 individuals. However, further investigation on 12 S rDNA and ND5 genes provided the useful polymorphic information for those 5 individuals. Although the experiment had been carried out to produce SCNT calves without previous investigation of mtDNA polymorphism, polymorphic mtDNA sequences provided interesting information that discriminated individuals, even those from the same donor cells. In addition, we could distinguish the 2nd generations produced by AI combinations using SCNT donors and SCNT progeny as the dams and/or the sires when combined molecular data obtained from MS genotypes and mtDNA polymorphisms were derived. These results suggested that mtDNA polymorphisms might supply the critical information for identification and traceability for SCNT-derived calves when combined with MS data. This work received grant support from the Agenda Program (No. 200901FHT010305191), Rural Development Administration, Republic of Korea.

Five coding region polymorphism of mitochondrial DNA in Chinese Han population of Yanbian area

To investigate the mitochondrial DNA (mtDNA) five coding region sequence polymorphisms encompassing positions nt3954-4506, nt5218-5974, nt7942-8711, nt10296-10653, and nt14496-14867 in Chinese Han population of Yanbian area, Jilin province. Polymerase chain reaction (PCR) and direct sequencing method were used to detect the haplotype distribution of mtDNA coding region in 200 unrelated Chinese Han individuals. One hundred and ten haplotypes were observed in the 200 individuals. The gene diversity was 0.9879 and the random match probability was 0.0171. Compared with the Anderson's sequence,81 nucleotide variants were obtained,of which 66 were previously registered in MITOMAP,and 15 were novel. The obtained data suggest that these sequence polymorphisms are valuable genetic markers for personal identification when added to mtDAN control region investigation, and thus could be used as basic data for the forensic application in Chinese Han population.

Mitochondrial DNA patterns in the Macaronesia islands: Variation within and among archipelagos

Macaronesia covers four Atlantic archipelagos: the Azores, Madeira, the Canary Islands, and the Cape Verde islands. When discovered by Europeans in the 15th century, only the Canaries were inhabited. Historical reports highlight the impact of Iberians on settlement in Macaronesia. Although important differences in their settlement are documented, its influence on their genetic structures and relationships has yet to be ascertained. In this study, the hypervariable region I (HVRI) sequence and coding region polymorphisms of mitochondrial DNA (mtDNA) in 623 individuals from the Azores (120) and Canary Islands (503) were analyzed. Combined with published data, these give a total of 1,542 haplotypes from Macaronesia and 1,067 from the Iberian Peninsula. The results obtained indicate that Cape Verde is the most distinctive archipelago, with an mtDNA pool composed almost exclusively of African lineages. However, the other archipelagos present an mtDNA profile dominated by the presence of West-Eurasian mtDNA haplogroups with African lineages present in varying proportions. Moreover, no signs of integration of typical Canarian U6 lineages in the other archipelagos were detected. The four Macaronesia archipelagos currently have differentiated genetic profiles, and the Azores present the highest intra-archipelago differentiation and the lowest values of diversity. The analyses performed show that the present-day genetic profile of the Macaronesian archipelagos was mainly determined by the initial process of settlement and further microdifferentiation probably as a consequence of the small population size of some islands. Moreover, contacts between archipelagos seem to have had a low impact on the mtDNA genetic pool of each archipelago.

Genetic characterization of an unknown and endangered native population of the Nile tilapia Oreochromis niloticus (Linnaeus, 1758) (Cichlidae; Teleostei) in the Loboi Swamp (Kenya)

Nuclear and mitochondrial DNA polymorphism were studied in a number of natural populations of the Nile tilapia Oreochromis niloticus (Cichlidae; Teleostei) from East Africa in order to determine the origin of a recently discovered population from a warm water spring, the Lake Bogoria Hotel Spring, an affluent of the Loboi Swamp. This population was initially considered to have been introduced from other sites within the region. Its significant and unique genetic variability (high microsatellite and mtDNA polymorphism, highly significant F st values and the presence of private alleles) indicate however that it is an entirely new and formerly unknown natural population that had escaped earlier studies of this species. This natural population, that represents a significant genetic resource, is threatened by extensive human encroachment of the Loboi Swamp.

MtDNA G10398A variant in African-American women with breast cancer provides resistance to apoptosis and promotes metastasis in mice

We investigated the effect of the mitochondrial DNA (mtDNA) polymorphism G10398A found in African-American women with aggressive breast cancer on apoptosis and tumorigenesis. We generated human cytoplasmic hybrid (cybrid) by repopulation of recipient rho(0) cells (devoid of mtDNA) with donor mtDNA derived from patients with breast cancer harboring the G10398A polymorphism. We investigated a number of functional phenotypes of the G10398A cybrid. The G10398A cybrid showed a slower proliferation rate and progression through the cell cycle, as well as increased complex I activity, increased levels of reactive oxygen species and depolarized mitochondria. The G10398A cybrid also showed resistance to apoptosis triggered by etoposide. Resistance to apoptosis was mediated by Akt activation. In addition, our studies showed that the G10398A cybrid cells form an increased number of anchorage-independent colonies in vitro and metastases in mice. Together our studies suggest that the G10398A variant confers resistance to apoptosis and promotes metastasis.