LENGTH MUTATIONS IN HUMAN MITOCHONDRIAL DNA

ABSTRACT By high-resolution, restriction mapping of mitochondrial DNAs purified from 112 human individuals, we have identified 14 length variants caused by small additions and deletions (from about 6 to 14 base pairs in length). Three of the 14 length differences are due to mutations at two locations within the D loop, whereas the remaining 11 occur at seven sites that are probably within other noncoding sequences and at junctions between coding sequences. In five of the nine regions of length polymorphism, there is a sequence of five cytosines in a row, this sequence being comparatively rare in coding DNA. Phylogenetic analysis indicates that, in most of the polymorphic regions, a given length mutation has arisen several times independently in different human lineages. The average rate at which length mutations have been arising and surviving in the human species is estimated to be many times higher for noncoding mtDNA than for noncoding nuclear DNA. The mystery of why vertebrate mtDNA is more prone than nuclear DNA to evolve by point mutation is now compounded by the discovery of a similar bias toward rapid evolution by length mutation.

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Mitochondrial DNA Methylation and Human Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22094594 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4594

Author(s):

Andrea Stoccoro ◽

Fabio Coppedè

Keyword(s):

Dna Methylation ◽

Mitochondrial Dna ◽

Mitochondrial Genome ◽

Nuclear Dna ◽

Epigenetic Modification ◽

Nuclear Genome ◽

Epigenetic Modifications ◽

Human Diseases ◽

Loop Region ◽

D Loop

Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases. Moreover, environmental factors, as well as nuclear DNA genetic variants, have been found to impair mtDNA methylation patterns. Some authors failed to find DNA methylation marks in the mitochondrial genome, suggesting that it is unlikely that this epigenetic modification plays any role in the control of the mitochondrial function. On the other hand, several other studies successfully identified the presence of mtDNA methylation, particularly in the mitochondrial displacement loop (D-loop) region, relating it to changes in both mtDNA gene transcription and mitochondrial replication. Overall, investigations performed until now suggest that methylation and hydroxymethylation marks are present in the mtDNA genome, albeit at lower levels compared to those detectable in nuclear DNA, potentially contributing to the mitochondria impairment underlying several human diseases.

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Genetic Diversities and Historical Dynamics of Native Ethiopian Horse Populations (Equus caballus) Inferred from Mitochondrial DNA Polymorphisms

Genes ◽

10.3390/genes12020155 ◽

2021 ◽

Vol 12 (2) ◽

pp. 155

Author(s):

Kefena Effa ◽

Sonia Rosenbom ◽

Jianlin Han ◽

Tadelle Dessie ◽

Albano Beja-Pereira

Keyword(s):

Genetic Diversity ◽

Mitochondrial Dna ◽

Genetic Differentiation ◽

Sequence Divergence ◽

Dna Polymorphisms ◽

Base Pairs ◽

Feral Horses ◽

Domestic Horses ◽

D Loop ◽

Diversity Estimates

Matrilineal genetic diversity and relationship were investigated among eight morphologically identified native Ethiopian horse populations using polymorphisms in 46 mtDNA D-loop sequences (454 base pairs). The horse populations identified were Abyssinian, Bale, Borana, Horro, Kafa, Kundido feral horses, Ogaden and Selale. Mitochondrial DNA D-loop sequences were characterized by 15 variable sites that defined five different haplotypes. All genetic diversity estimates, including Reynolds’ linearized genetic distance, genetic differentiation (FST) and nucleotide sequence divergence (DA), revealed a low genetic differentiation in native Ethiopian horse populations. However, Kundido feral and Borana domestic horses were slightly diverged from the rest of the Ethiopian horse populations. We also tried to shed some light on the matrilineal genetic root of native Ethiopian horses from a network constructed by combining newly generated haplotypes and reference haplotypes deposited in the GenBank for Eurasian type Turkish Anatolian horses that were used as a genetic conduit between Eurasian and African horse populations. Ninety-two haplotypes were generated from the combined Ethio-Eurasian mtDNA D-loop sequences. A network reconstructed from the combined haplotypes using Median-Joining algorithm showed that haplotypes generated from native Ethiopian horses formed separate clusters. The present result encourages further investigation of the genetic origin of native African horses by retrieving additional mtDNA sequences deposited in the GenBank for African and Eurasian type horses.

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Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction

Molecular and Cellular Biology ◽

10.1128/mcb.2.1.30-41.1982 ◽

1982 ◽

Vol 2 (1) ◽

pp. 30-41

Author(s):

N A Oliver ◽

D C Wallace

Keyword(s):

Mitochondrial Dna ◽

Restriction Site ◽

Mitochondrial Protein ◽

Mitochondrial Protein Synthesis ◽

Human Mitochondrial Dna ◽

Ht1080 Cells ◽

Mitochondrial Dnas ◽

A Cell ◽

Dna Restriction ◽

Restriction Site Polymorphisms

Two mitochondrially synthesized marker polypeptides, MV-1 and MV-2, were found in human HeLa and HT1080 cells. These were assigned to the mitochondrial DNA in HeLa-HT1080 cybrids and hybrids by demonstrating their linkage to cytoplasmic genetic markers. These markers include mitochondrial DNA restriction site polymorphisms and resistance to chloramphenicol, an inhibitor of mitochondrial protein synthesis. In the absence of chloramphenicol, the expression of MV-1 and MV-2 in cybrids and hybrids was found to be directly proportional to the ratio of the parental mitochondrial DNAs. In the presence of chloramphenicol, the marker polypeptide linked to the chloramphenicol-sensitive mitochondrial DNA continued to be expressed. This demonstrated that resistant and sensitive mitochondrial DNAs can cooperate within a cell for gene expression and that the CAP-resistant allele was dominant or codominant to sensitive. Such cooperation suggests that mitochondrial DNAs can be exchanged between mitochondria.

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Genetic diversity study in Hungarian coldblooded horses

Acta Agraria Debreceniensis ◽

10.34101/actaagrar/73/1622 ◽

2017 ◽

pp. 29-34

Author(s):

Nikolett Csizmár ◽

Sándor Mihók ◽

András Jávor ◽

Szilvia Kusza

Keyword(s):

High Performance ◽

Nucleotide Diversity ◽

Base Pairs ◽

Loop Region ◽

Horse Breeding ◽

D Loop ◽

Hungarian Population ◽

Genetic Diversity Study ◽

Feeding Technology ◽

Diversity Study

Because of the feeding technology innovation, accelerated transport and communication facilities breeds of high performance breeds replaced local autochone breeds worldwide. These latter species however have an important role in gene conservation. Hungarian cold-blooded horse breeding stock are lacking pedigree, the actual founder breed mares are not known. For this reason, it is an major priority defining the genetic backround of the existing flock, for that breeding could operate with purposeful using of origin maternal founders. In the present study 195 cold-blooded Hungarian mares tail and mane sample were analized. Our analysis was carried out between 15531–15752 base pairs in mithocrondial DNA D-loop region, which reported a total of 222 base pairs. Fourtyone polymorphic sites were determined, which resulted in 39 haplotypes (h=39). The average pairwise differences were k=6.825. High haplotype and nucleotide diversity values were observed (Hd=0.968±0.003, π=0.026±0.003). Based on the previously defined variable positions of haplotypes defined by Jansen et al (2002), we groupped our haplotypes into haplogroups. 23 percent of the studied population (45 mares) belonged to haplogroup F1. Nearly 97% of the analyzed population was classified into one of eight haplogroups defined by Jansen.et al. (2002). This study gives genetic information nearly 25% of the Hungarian population. Another possibility would be patterning more mares or involving more genetic marker in the study which will assuming the possibility of a more comprehensive analysis.

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Reconstruction of complexes of histone and superhelical nuclear DNA

Journal of Cell Science ◽

10.1242/jcs.50.1.209 ◽

1981 ◽

Vol 50 (1) ◽

pp. 209-224

Author(s):

J.M. Levin ◽

P.R. Cook

Keyword(s):

Nuclear Dna ◽

Micrococcal Nuclease ◽

Base Pairs ◽

The Core ◽

Ionic Detergent ◽

Nuclear Rna ◽

Core Histones ◽

Non Destructive ◽

Rna And Dna ◽

General Method

When HeLa cells are lysed in solutions containing a non-ionic detergent and 2 M-NaCl, structures are released that retain many of the morphological features of nuclei. These nucleoids contain all the nuclear RNA and DNA but few of the proteins characteristic of chromatin. Their DNA is supercoiled and so intact. Using a simple and rapid procedure we have reconstructed nucleohistone complexes from nucleoids and the ‘core’ histones without breaking the DNA. We have probed the integrity and structure of the reconstructed complexes using a non-destructive fluorometric approach, which provides a general method for detecting agents that bind to DNA and alter its supercoiling. The superhelical status of the DNA in the reconstructed complexes is indistinguishable from that found in control nucleoids containing core histones. Experiments with micrococcal nuclease confirm that the DNA in the reconstructed complexes is organized into nucleosome-like structures. These, however, are spaced 145 base-pairs apart and not 200 base-pairs apart as is found in native chromatin.

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The heart in neuromuscular disease: primary mitochondrial diseases

ESC CardioMed ◽

10.1093/med/9780198784906.003.0369 ◽

2018 ◽

pp. 1528-1530

Author(s):

Denis Duboc

Keyword(s):

Neuromuscular Disease ◽

Nuclear Dna ◽

Single Cells ◽

Mitochondrial Diseases ◽

Respiratory Chain Complexes ◽

Base Pairs ◽

Daughter Cells ◽

Dna Molecule ◽

Chain Complexes ◽

Genes Encoding

Mitochondria are responsible for energy production in most eukaryotic cells. Each cell contains at least one mitochondrion and every mitochondrion contains two to ten copies of a circular DNA molecule (mitochondrial DNA or mtDNA). Cardiomyocytes contain approximately 10,000 mtDNA copies. MtDNA is composed of around 16,500 base pairs and 37 genes encoding 13 subunits of the respiratory chain complexes I, III, IV, and V, 22 mitochondrial tRNAs and 2 rRNAs. With each cell division, mitochondria and mtDNA are randomly distributed to daughter cells. In humans, mitochondria are inherited exclusively from the mother. In healthy people mtDNA copies are usually identical at birth (homoplasmy) but with ageing, mtDNA is particularly prone to somatic mutation because, unlike nuclear DNA, it is continuously replicated, even in non-dividing tissues such as myocardium. This can lead to the propagation of somatic mutations within single cells by a process called clonal expansion. In addition, mtDNA lacks an extensive DNA repair mechanism.

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Sequence deduced physical properties in the D-loop region common to five vertebrate mitochondrial DNAs

Journal of Theoretical Biology ◽

10.1016/s0022-5193(87)80252-7 ◽

1987 ◽

Vol 124 (1) ◽

pp. 57-69 ◽

Cited By ~ 8

Author(s):

Bernard Mignotte ◽

Dominique Dunon-Bluteau ◽

Claude Reiss ◽

Jean-Claude Mounolou

Keyword(s):

Physical Properties ◽

Loop Region ◽

Mitochondrial Dnas ◽

D Loop

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Length mutations in human mitochondrial DNA: direct sequencing of enzymatically amplified DNA

Nucleic Acids Research ◽

10.1093/nar/15.2.529 ◽

1987 ◽

Vol 15 (2) ◽

pp. 529-541 ◽

Cited By ~ 231

Author(s):

Lisa A. Wrischnik ◽

Russell G. Higuchi ◽

Mark Stoneking ◽

Henry A. Erlich ◽

Norman Arnheim ◽

...

Keyword(s):

Mitochondrial Dna ◽

Direct Sequencing ◽

Human Mitochondrial Dna ◽

Length Mutations

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VARIAN NON-DELESI 9 PASANG BASA DNA MITOKONDRIA MANUSIA SAMPEL FORENSIK BALI

Jurnal Pengajaran Matematika dan Ilmu Pengetahuan Alam ◽

10.18269/jpmipa.v6i1.373 ◽

2005 ◽

Vol 6 (1) ◽

pp. 74

Author(s):

Gun Gun Gumilar ◽

A. Saifuddin Noer

Keyword(s):

Gel Electrophoresis ◽

Secondary Data ◽

Primary Data ◽

Agarose Gel Electrophoresis ◽

Chain Reaction ◽

Base Pairs ◽

Human Mitochondrial Dna ◽

Deletion Variant ◽

Forensic Samples ◽

Polymerase Chain

One of human mitochondrial DNA (mtDNA) variant is a 9 base pairs (bp) deletion in the COII/tRNALys intergenic region. In construction mtDNA nomenclature, 9-bp deletion database consist of primary and secondary data is needed, including Bali bombing forensic samples. Here we report a 9-bp non- deletion mtDNA variant from Bali bombing forensic samples to complete primary data. Polymerase Chain Reaction (PCR) technique with 2 set primer was used to detect 9-bp deletion. The PCR result was detected by agarose gel electrophoresis, which showed two bands (0.1 and 0.4 kb) for non-deletion variant control, and one band (0.4 kb) for deletion variant control. If the sample has 9-bp deletion, only one of the primer pairs could amplify a fragment of 0.4 kb. If the sample does not have 9-bp deletion, the other primer pair will amplify a 0.1 kb product. The result showed that none of the 24 samples has 9-bp deletion. These results are contributed to the human mtDNA database and nomenclature construction. Keywords: mtDNA, 9-bp deletion, PCR

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