Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “mtDNA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed2004

A call for mtDNA data quality control in forensic science.

There is increasing evidence that many of the mitochondrial DNA (mtDNA) databases published in the fields of forensic science and molecular anthropology are flawed. An a posteriori phylogenetic analysis of the sequences could help to eliminate most of the errors and thus greatly improve data quality. However, previously published caveats and recommendations along these lines were not yet picked up by all researchers. Here we call for stringent quality control of mtDNA data by haplogroup-directed database comparisons. We take some problematic databases of East Asian mtDNAs, published in the Journal of Forensic Sciences and Forensic Science International, as examples to demonstrate the process of pinpointing obvious errors. Our results show that data sets are not only notoriously plagued by base shifts and artificial recombination but also by lab-specific phantom mutations, especially in the second hypervariable region (HVR-II).

DNA Fingerprinting↗
PubMed2005

Evaluating the forensic informativeness of mtDNA haplogroup H sub-typing on a Eurasian scale.

The impact of phylogeographic information on mtDNA forensics has been limited to the quality control of published sequences and databases. In this work we use the information already available on Eurasian mtDNA phylogeography to guide the choice of coding-region SNPs for haplogroup H. This sub-typing is particularly important in forensics since, even when sequencing both HVRI and HVRII, the discriminating power is low in some Eurasian populations. We show that a small set (eight) of coding-region SNPs resolves a substantial proportion of the identical haplotypes, as defined by control-region variation alone. Moreover, this SNP set, while substantially increasing the discriminating efficiency in most Eurasian populations by roughly equal amounts, discloses population-specific profiles.

Asia↗
PubMed2004

Segregation pattern and biochemical effect of the G3460A mtDNA mutation in 27 members of LHON family.

Inheritance and expression of mitochondrial DNA (mtDNA) mutations are crucial for the pathogenesis of Leber hereditary optic neuropathy (LHON). We have investigated the segregation and functional consequences of G3460A mtDNA mutation in 27 members of a three-generation family with LHON syndrome. Specific activity of respiratory chain complex I in platelets was reduced in average to 56%, but no direct correlation between the mutation load and its biochemical expression was found. Heteroplasmy in blood, platelets and hair follicles varied from 7% to 100%. Segregation pattern exhibited tissue specificity and influence of different nuclear backgrounds in four branches of the pedigree. Longitudinal analysis revealed a significant (p=0.02) decrease in blood mutation load. Although enzyme assay showed reduction of complex I activity, our results give additional support to the hypothesis that expression of LHON mutation depends on complex nuclear-mitochondrial interaction.

Alanine↗
PubMed2004

Control region sequences for East Asian individuals in the Scientific Working Group on DNA Analysis Methods forensic mtDNA data set.

The Scientific Working Group on DNA Analysis Methods (SWGDAM) mitochondrial DNA (mtDNA) population data set is used to infer the relative rarity of mtDNA profiles obtained from evidence samples and of profiles used to identify missing persons. In this study, the East Asian haplogroup patterns in the SWGDAM data sets were analyzed in a phylogenetic context to determine relevant single nucleotide polymorphisms (SNPs) and to describe haplogroup distributions for Asians (n = 753; with a breakdown of individuals from China n = 356, Korea n = 182, Japan n = 163, and Thailand n = 52). We focus on the patterns observed in the SWGDAM Chinese data set and refer to interesting differences in the smaller subgroup data sets for the other East Asian populations (Japanese, Korean, and Thai). A total of 218 SNPs were observed in the data set, including 37 observed positions not previously reported. In the largest of the East Asian SWGDAM data sets (Chinese), these SNPs ranged from having 1 to 29 changes in the phylogenetic tree, with site 16519 being the most variable. On average there were 4.5 changes for a character on the tree. The most variable sites (with 14 or more changes each listed from fastest to slowest) observed were 16519 (L = 29), 16311 (L = 27), 152 (L = 24), 146 (L = 21), 16172 (L = 17), 16189 (L = 17), 195 (L = 16), 16362 (L = 15), 16093 (L = 14), 16129 (L = 14) and 150 (L = 14). These rapidly changing sites are consistent with other published analyses. Only 28 SNPs are needed to identify all clusters containing 1% (n = 7) or more individuals in the East Asian data set. All 36 haplogroups previously observed in East Asian populations were also seen in the SWGDAM data sets and include: A, B, B4, B4a, B4b, B5a, B5b, C, D, D4, D4a, D4b, D5, D5a, F, F1, F1a, F1b, F1c, F2a, G2, G2a, M, M7a1, M7b, M7b1, M7b2, M7c, M8a, M9, M10, N9a, R, R9a, Y, and Z. Haplogroups A, B4a, D4, and F1a were the most commonly observed clusters in the Chinese data set (the largest of the data sets) with each of these occurring in more than 6% of the samples in the data set. The next most common haplogroups in the Chinese data set include the clusters C, M7b1, and N9a with each observed at frequencies greater than or equal to 4%. European Caucasian, and African haplogroups were rarely observed within the East Asian data sets. The various analyses revealed that the data set was similar to published East Asian data sets such as those from Han Chinese.

Asian People↗
PubMed2005

The common deletion found in patient reexamined after 33 years and comparison with complete mtDNA sequences of maternal relatives.

In 1966, a male (17 years old) was clinically examined at the National Institutes of Health (NIH) and diagnosed with Idiopathic Progressive External Ophthalmoplegia (IPEO). A muscle biopsy showing ragged-red fibers implicated mitochondrial involvement. Since the sequence of human mitochondrial DNA (mtDNA) was not determined until 1981, no genetic confirmation of the disease was possible at that time. In 1999, clinical reexamination and sequencing the entire mtDNA of the patient and living maternal relatives (mother and brother) indicated a progressive mitochondrial myopathy and the presence of the 4977 base pair (bp) deletion (the common deletion) in the patient.

Adolescent↗
PubMed2004

Monomelic amyotrophy associated with the 7472insC mutation in the mtDNA tRNASer(UCN) gene.

We describe a 49-year-old male patient who experienced progressive amyotrophy with no sensorial abnormality in the left arm since 45 years of age. The neuromuscular syndrome was identical to that known as Hirayama disease, a rare form of focal lower motor neuron disease affecting the C7-C8-T1 metamers of the spinal cord. Asymmetric neurosensorial hearing loss was present since age 35 in the patient, and was also documented in an elder sister and in the mother. A muscle biopsy showed cytochrome c oxidase (COX) negative fibers but no ragged-red fibers, and mild reduction of COX was confirmed biochemically. The patient was found to have high levels of a known pathogenic mutation of mtDNA, the 7472insC in the gene encoding the tRNA(Ser(UCN)). Investigation on several family members showed a correlation between mutation load and clinical severity. This is the second report documenting the association of lower motor neurone involvement with a specific mtDNA.

DNA, Mitochondrial↗
PubMed2005

mtDNA mutations and common neurodegenerative disorders.

The incidence and prevalence of Alzheimer's disease (AD) and Parkinson's disease (PD) are increasing as the population ages. Both disorders have been associated with oxidative stress and mitochondrial dysfunction, and it has been proposed that mutations in the mitochondrial genome have a key role in neurodegeneration in AD and PD patients. Two recent publications propose that heteroplasmic mtDNA mutations are involved in AD and PD. However, when these new studies are considered in relation to the sum of previous evidence, the role of mtDNA mutations in the development of either AD or PD still remains to be established.

Alzheimer Disease↗
PubMed2001

Inhibition of mitochondrial protein synthesis promotes autonomous regulation of mtDNA expression and generation of a new mitochondrial RNA species.

Mammalian mitochondria are known to proliferate in response to several stimuli. Proliferation requires an increase in expression of genes encoding proteins involved in mitochondrial biogenesis, as well as in the replication and expression of mitochondrial DNA (mtDNA). In contrast, we report that inhibiting mitochondrial protein synthesis causes a modulation in mtDNA gene expression without the concomitant increase in proliferative markers. Further, inhibition results in the production of a previously unidentified light-strand mitochondrial RNA that spans the entire displacement loop, the function of which is currently unknown.

Base Sequence↗
PubMed2007

Difficulties and possible solutions in the genetic management of mtDNA disease in the preimplantation embryo.

Families who have had a child die of a severe, maternally inherited mitochondrial DNA (mtDNA) disease are usually desperate to avoid having further affected children. Here we discuss the problems of applying classical genetic management to mtDNA diseases (Poulton and Turnbull, 2000) and the biology underlying these problems. We explain why these disorders have lagged so far behind the genetics revolution. We then outline the directions in which management is likely to develop, including the use of preimplantation genetic diagnosis (PGD).

Animals↗
PubMed2003

Pathogenic expression of homoplasmic mtDNA mutations needs a complex nuclear-mitochondrial interaction.

Here we define a category of human, maternally inherited disorders that are characterized by a homoplasmic mtDNA pathogenic mutation with variable penetrance and a stereotypical clinical expression, usually restricted to a single tissue. Examples of such disorders include Leber's hereditary optic neuropathy, mitochondrial non-syndromic sensorineural hearing loss, and a form of mitochondrial hypertrophic cardiomyopathy. The mtDNA mutation is necessary, but not sufficient to induce the pathology, and multiple lines of evidence suggest a two-locus genetic model involving a primary mitochondrial mutation and a nuclear modifier. The nuclear modifier does not induce any pathology per se, but it contributes to the pathogenic effect of the mitochondrial mutation. The nuclear modifier could be a common functional polymorphism in a tissue-specific protein, possibly with mitochondrial location.

Animals↗
PubMed1998

Evaluation of a decontamination protocol for hair shafts before mtDNA sequencing.

Mitochondrial DNA (mtDNA) sequencing is a powerful and sensitive method to identify the donor of shed hairs found at a crime scene. Because of the low amounts of DNA in shed hair and the sensitivity of PCR, contaminating cells (e.g. saliva, blood), sometimes present on these hairs, will be co-amplified. This will result in ambiguous sequencing results and might even lead to erroneous exclusions of suspects. We have evaluated a strategy for effectively removing saliva and blood contamination from hair samples. Unambiguous mtDNA results were obtained by incubating the hair samples in a differential lysis buffer (which contains no DTT) prior to DNA extraction. Since the nuclear DNA of the hair root is affected, this procedure should be restricted to hair shaft proportions.

Blood↗
PubMed1998

Reproducibility of mtDNA analysis between laboratories: a report of the European DNA Profiling Group (EDNAP).

The aim of this collaborative exercise was to determine whether uniformity of mtDNA sequencing results could be achieved among different EDNAP laboratories. Laboratories were asked to sequence mtDNAHV1 region (16024-16365) from three bloodstains, proceeding in accordance with the protocol and strategies currently used in each individual laboratory. Cycle sequencing was used by 11 laboratories and solid phase single stranded sequencing was used by one laboratory. Different PCR strategies and PCR conditions were used by the different laboratories. Three laboratories used semi-nested PCR, two nested PCR, three direct amplification of HV1 and four amplification of overlapping fragments covering the HV1 region. Despite the diversity of methodologies used, all the laboratories reported the same results. The successful result of this exercise shows that PCR based mtDNA typing by automated sequencing is a valid, robust and reliable means of forensic identification despite the different strategies and methodologies used by the different laboratories.

DNA Fingerprinting↗
PubMed2006

The genetic diversity of mtDNA D-loop and the origin of Chinese goats.

The complete sequences of mitochondrial DNA D-loop of 128 individuals in nine Chinese goat (Capra hircu) breeds were analyzed by DNA sequencing technology. The results show that the length of mtDNA D-loop in Chinese goats is 1,212-1,213 bp. There are 102 polymorphic sites, accounting for 8.42% of 1,212 bp sequence. Ninety-two mtDNA haplotypes were determined. The haplotype diversity and nucleotide diversity are 0.9333-1.0000 and 0.7062%-1.8265%, respectively. The results indicate that the genetic diversity of Chinese goats is very abundant. The NJ tree indicates that Chinese goats have two types of maternal origins from lineage A and lineage B. The possibility of lineage B originating from China is also discussed.

Animals↗
PubMed2006

Study on tandem repeat sequence variation in sheep mtDNA D-loop region.

The 75-nt-long tandem repeat sequence in the control region of mtDNA of 77 individuals, of which 69 were from different indigenous sheep breeds in China and 8 were from imported breeds, was sequenced and analyzed to investigate the origin and differentiation of Chinese indigenous sheep breeds and also the genetic diversities and relationships among them. A total of 28 variable sites were detected within 309 repeated sequences, among which 7 sites were singleton variable sites with two variants, 1 site was a singleton variable site with three variants, and 20 sites were parsimony informative sites with two variants. A total of 63 haplotypes were sorted from 28 polymorphic sites, among which two main and basic haplotypes, namely, Hap 1 and Hap 3 were present at a much higher proportion, at 12.94% and 30.42%, respectively. It could be inferred that Chinese indigenous sheep breeds originated from two maternal ancestors because of the maternal inheritance characteristics of the mtDNA. Altay sheep and Kazakstan sheep are closely related and do not differentiate significantly. Mongolian sheep and Ujumuqin sheep also share a close relationship. Tibetan sheep, Mongolian sheep, and Ujumuqin sheep have lower genetic diversity than Altay sheep and Kazakstan sheep.

Animals↗
PubMed2003

Phylogeography of pipistrelle-like bats within the Canary Islands, based on mtDNA sequences.

Evolution of three Canary Island Vespertilionid bat species, Pipistrellus kuhlii, Pipistrellus maderensis, and Hypsugo savii was studied by comparison of approximately 1 kbp of mtDNA (from cytochrome b and 16S rRNA genes) between islands. mtDNA reveals that both P. kuhlii and P. maderensis exist in sympatry on Tenerife (and possibly other islands). Their morphological similarity explains why their co-occurrence had not been detected previously. Levels of sequence divergence are quite low within P. maderensis. Haplotypes were either identical or separated by </=2 mutational steps on two of the islands (La Gomera and El Hierro). However there is sufficient between-island divergence between haplotypes from Tenerife, La Palma, and La Gomera/El Hierro to suggest that they could represent three evolutionary significant units (ESU). H. savii has an overlapping island distribution but a contrasting phylogeographical pattern. Most significantly, sequence divergence is greatest between La Gomera and El Hierro (>/=12 mutational steps) indicating colonization of the latter from the former sometime during the last approximately 1.2 Ma, with low subsequent gene flow. Unlike P. maderensis the El Hierro population alone appears to represent an ESU. The H. savii haplotypes detected in Gran Canaria and Tenerife are identical or separated by 1 mutational step.

Animals↗
PubMed2003

mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency.

Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to elucidate the mechanism of tissue specificity in the disease we have investigated the expression of the mitochondrial deoxynucleotide carrier, the mtDNA content and the activity of TK2 in mitochondria of various tissues. Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency.

Animals↗
PubMed1999

Sequence polymorphism in the mtDNA HV1 region in Japanese and Chinese.

We investigated the nucleotide substitution and insertion/deletion polymorphism of the HV1 region in mtDNA by sequencing blood samples from 150 unrelated Japanese and 120 unrelated Chinese and revealed 108 sequence types from the Japanese group and 87 sequence types from the Chinese. Some substitutions were characteristic of East Asian populations as compared with data reported on Caucasian populations, and some were area-specific among East Asians. The level of genetic diversity and genetic identity revealed by this system was superior to that obtained by VNTR systems for nuclear DNA. These results show the usefulness of mtDNA sequencing in forensic examination for individual identification. We also found some sequence variations in the homopolymeric tract of cytosine (np16180-16194 in the Anderson's reference sequence) that might suggest some hints regarding the mechanisms for and the development of heteroplasmic length variations in this tract.

Journal Article↗