Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A novel 154-bp deletion in the human mitochondrial DNA control region in healthy individuals.

ABSTRACT: The biological role of the mitochondrial DNA (mtDNA) control region in mtDNA replication remains unclear. In a worldwide survey of mtDNA variation in the general population, we have identified a novel large control region deletion spanning positions 16154 to 16307 (m.16154_16307del154). The population prevalence of this deletion is low, since it was only observed in 1 out of over 120,000 mtDNA genomes studied. The deletion is present in a nonheteroplasmic state, and was transmitted by a mother to her two sons with no apparent past or present disease conditions. The identification of this large deletion in healthy individuals challenges the current view of the control region as playing a crucial role in the regulation of mtDNA replication, and supports the existence of a more complex system of multiple or epigenetically-determined replication origins.

SUBMITTER: Behar DM

PROVIDER: S-EPMC2697596 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A novel 154-bp deletion in the human mitochondrial DNA control region in healthy individuals.

Behar Doron M DM Blue-Smith Jason J Soria-Hernanz David F DF Tzur Shay S Hadid Yarin Y Bormans Concetta C Moen Alexander A Tyler-Smith Chris C Quintana-Murci Lluis L Wells R Spencer RS

Human mutation 20081201 12

The biological role of the mitochondrial DNA (mtDNA) control region in mtDNA replication remains unclear. In a worldwide survey of mtDNA variation in the general population, we have identified a novel large control region deletion spanning positions 16154 to 16307 (m.16154_16307del154). The population prevalence of this deletion is low, since it was only observed in 1 out of over 120,000 mtDNA genomes studied. The deletion is present in a nonheteroplasmic state, and was transmitted by a mother t ...[more]

PMID: 18629826

Similar Datasets

Detection of 40 bp insertion-deletion (INDEL) in mitochondrial control region among sambar (Rusa unicolor) populations in India.

Project description:The mitochondrial DNA (mtDNA) control region is extensively used in the phylogeography of species. We examined sequence variations in the mtDNA control region of sambar (Rusa unicolor) populations from the South, Central and North India.Most of the samples collected from the south India exhibited a 40 bp insertion in the mtDNA control region. This insertion was not observed in the North and Central Indian populations.This study provided a potential marker for molecular screening and identification of sambar populations in the form of a distinct 40 bp insertion. Some populations in South India did not exhibit this insertion. It indicates that there could be an ecological barrier that might be preventing the expansion of insertion-positive sambar population.

| S-EPMC4617744 | biostudies-literature

Correlation of the 4977 bp mitochondrial DNA deletion with human sperm dysfunction.

Project description:BACKGROUND: Several studies have examined the association between mitochondrial DNA (mtDNA) deletions, in particular the "common" 4977-bp deletion, and human sperm dysfunction, but have produced contradictory results. FINDINGS: Here we show that PCR slippage and primer miss-match to nuclear DNA may lead to overestimates in the frequency of deletions. Our investigation resolves this issue and gives strong negative correlation between the proportion of the "common" deletion and sperm motility. Furthermore, for the first time, we present data which reinforce the hypothesis for a negative correlation between the mtDNA "common" deletion and fertilization efficiency of spermatozoa. CONCLUSION: The present analysis resolves several literature inconsistencies and opens the way for diagnostic use of the "common" deletion as a molecular indicator of sperm fertility potential.

| S-EPMC2642850 | biostudies-other

Mitochondrial DNA 4977 bp Deletion in Peripheral Blood Is Associated With Polycystic Ovary Syndrome.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder worldwide. We aimed to examine the associations of two mitochondrial DNA (mtDNA) biomarkers in the peripheral blood, mtDNA copy number (CN), and mtDNA4977 deletion rate (DR), with PCOS in a clinical setting.MethodsWe performed a study involving 263 women with PCOS and 326 age-matched controls between June 2015 and June 2019. The mtDNA CN and mtDNA4977 DR were measured using multiplex probe-based qPCR. The associations of the mtDNA CN and mtDNA4977 DR with the risk of PCOS were estimated using logistic regression.ResultsAnalysis of the associations between mtDNA biomarkers and PCOS indicate that the mtDNA CN (P = 0.003) and mtDNA4977 DR (P < 0.001) in PCOS patients were significantly higher than those in the controls. After adjusting for the body mass index, luteinizing hormone/follicle-stimulating hormone ratio, and testosterone level, only higher mtDNA4977 DR was associated with PCOS (odds ratio 1.053, 95% confidence interval 1.024 to 1.083; P < 0.001). The linear dose-response trends of the mtDNA4977 DR were also supported by the quartile analysis.ConclusionMultivariable models suggest that mtDNA4977 DR levels are strongly associated with PCOS and represent an independent risk factor for PCOS. Further investigation of the utility of mtDNA as a biomarker for PCOS is warranted.

| S-EPMC8296803 | biostudies-literature

Increases in mitochondrial DNA content and 4977-bp deletion upon ATM/Chk2 checkpoint activation in HeLa cells.

Project description:Activation of the Mec1/Rad53 damage checkpoint pathway influences mitochondrial DNA (mtDNA) content and point mutagenesis in Saccharomyces cerevisiae. The effects of this conserved checkpoint pathway on mitochondrial genomes in human cells remain largely unknown. Here, we report that knockdown of the human DNA helicase RRM3 enhances phosphorylation of the cell cycle arrest kinase Chk2, indicating activation of the checkpoint via the ATM/Chk2 pathway, and increases mtDNA content independently of TFAM, a regulator of mtDNA copy number. Cell-cycle arrest did not have a consistent effect on mtDNA level: knockdown of cell cycle regulators PLK1 (polo-like kinase), MCM2, or MCM3 gave rise, respectively, to decreased, increased, or almost unchanged mtDNA levels. Therefore, we concluded that the mtDNA content increase upon RRM3 knockdown is not a response to delay of cell cycle progression. Also, we observed that RRM3 knockdown increased the levels of reactive oxygen species (ROS); two ROS scavengers, N-acetyl cysteine and vitamin C, suppressed the mtDNA content increase. On the other hand, in RRM3 knockdown cells, we detected an increase in the frequency of the common 4977-bp mtDNA deletion, a major mtDNA deletion that can be induced by abnormal ROS generation, and is associated with a decline in mitochondrial genome integrity, aging, and various mtDNA-related disorders in humans. These results suggest that increase of the mitochondrial genome by TFAM-independent mtDNA replication is connected, via oxidative stress, with the ATM/Chk2 checkpoint activation in response to DNA damage, and is accompanied by generation of the common 4977-bp deletion.

| S-EPMC3393681 | biostudies-literature

Polymorphisms of mitochondrial DNA control region are associated to endometriosis.

Project description:PURPOSE:Polymorphisms in the control region of mitochondrial DNA (mtDNA) can affect generation of reactive oxygen species and impact in the pathogenesis of endometriosis. This study investigated the association of mtDNA polymorphisms with endometriosis. METHODS:Patients were divided in two groups: endometriosis (n = 90) and control (n = 92). Inclusion criteria were as follows: women between 18 and 50 years, with histological diagnosis and surgical staging of endometriosis (endometriosis group) or undergoing gynecological surgery for tubal ligation, leiomyoma, or ovarian cysts, with no evidence of endometriosis (control group). DNA extraction was performed from peripheral blood. Sanger sequencing of mtDNA control region was performed, and polymorphisms were determined comparing the sequences obtained with the Cambridge Reference Sequence. RESULTS:The frequency of polymorphisms T16217C (14.4 and 5.4% of endometriosis and control group, respectively; p = 0.049) and G499A (13.3 vs. 4.3%; p = 0.038) was higher in the endometriosis group, while T146C (32.6 vs. 18.9%; p = 0.042) and 573.2C (5.6 vs. 29.3%; p < 0.001) were lower. No difference was observed in haplogroups between groups. CONCLUSION:mtDNA polymorphisms T16217C and G499A were associated with endometriosis, while T416C and 573.2C were shown to be associated with an absence of disease.

| S-EPMC5904057 | biostudies-literature

Growth Retardation in the Course of Fanconi Syndrome Caused by the 4977-bp Mitochondrial DNA Deletion: A Case Report.

Project description:Fanconi syndrome is one of the primary renal manifestations of mitochondrial cytopathies caused by mitochondrial DNA (mtDNA) mutation. The common 4977-bp mtDNA deletion has been reported to be associated with aging and diseases involving multiple extrarenal organs. Cases of Fanconi syndrome caused by the 4977-bp deletion were rarely reported previously. Here, we report a 6-year-old girl with growth retardation in the course of Fanconi syndrome. She had mild ptosis and pigmented retinopathy. Abnormal biochemical findings included low-molecular-weight proteinuria, normoglycemic glycosuria, increased urine phosphorus excretion, metabolic acidosis, and hypophosphatemia. Growth records showed that her body weight and height were normal in the first year and failed to thrive after the age of three. Using a highly sensitive mtDNA analysis methodology, she was identified to possess the common 4977-bp mtDNA deletion. The mutation rate was 84.7% in the urine exfoliated cells, 78.67% in the oral mucosal cells, and 23.99% in the blood sample. After three months of oral coenzyme Q10 and levocarnitine treatment in combination with standard electrolyte supplement, her condition was improved. This is a report of growth retardation as the initial major clinical presentation of Fanconi syndrome caused by the deletion of the 4977-bp fragment. Renal tubular abnormality without any other extrarenal dysfunction may be an initial clinical sign of mitochondrial disorders. Moreover, considering the heterogeneity of the phenotypes associated with mtDNA mutations, the risk of developing Kearns-Sayre syndrome (KSS) with age in this patient should be noted because she had ptosis, retinal involvement, and changes in the brain and skeletal muscle.

| S-EPMC8535084 | biostudies-literature

Feline non-repetitive mitochondrial DNA control region database for forensic evidence.

Project description:The domestic cat is the one of the most popular pets throughout the world. A by-product of owning, interacting with, or being in a household with a cat is the transfer of shed fur to clothing or personal objects. As trace evidence, transferred cat fur is a relatively untapped resource for forensic scientists. Both phenotypic and genotypic characteristics can be obtained from cat fur, but databases for neither aspect exist. Because cats incessantly groom, cat fur may have nucleated cells, not only in the hair bulb, but also as epithelial cells on the hair shaft deposited during the grooming process, thereby generally providing material for DNA profiling. To effectively exploit cat hair as a resource, representative databases must be established. The current study evaluates 402 bp of the mtDNA control region (CR) from 1394 cats, including cats from 25 distinct worldwide populations and 26 breeds. Eighty-three percent of the cats are represented by 12 major mitotypes. An additional 8.0% are clearly derived from the major mitotypes. Unique sequences are found in 7.5% of the cats. The overall genetic diversity for this data set is 0.8813±0.0046 with a random match probability of 11.8%. This region of the cat mtDNA has discriminatory power suitable for forensic application worldwide.

| S-EPMC2921450 | biostudies-literature

Mitochondrial DNA control region variation in a population sample from Thailand.

Project description:Mitochondrial DNA (mtDNA) control region sequences from hair samples of 213 individuals from Thailand were analyzed using Sanger sequencing. A total of 170 different haplotypes were identified, of which 146 occurred only once (unique haplotypes). The dataset showed a random match probability of 0.87% and a haplotype diversity of 0.9960. The samples were assigned to 85 different haplogroups with B5a, F1a1a, and M being the most frequent ones. Pairwise FST-values between this and other Southeast and East Asian populations revealed significant but relatively low differences, indicating a close relation. Heteroplasmic positions were observed in 12.2% of hair samples confirming the frequent appearance of heteroplasmic positions in hairs. This dataset will complement existing data as an mtDNA reference for forensic investigations.

| S-EPMC7417404 | biostudies-literature

Association of genetic variations in the mitochondrial DNA control region with presbycusis.

Project description:BackgroundThe prominent role of mitochondria in the generation of reactive oxygen species, cell death, and energy production contributes to the importance of this organelle in the intracellular mechanism underlying the progression of the common sensory disorder of the elderly, presbycusis. Reduced mitochondrial DNA (mtDNA) gene expression and coding region variation have frequently been reported as being associated with the development of presbycusis. The mtDNA control region regulates gene expression and replication of the genome of this organelle. To comprehensively understand of the role of mitochondria in the progression of presbycusis, we compared variations in the mtDNA control region between subjects with presbycusis and controls.MethodsA total of 58 presbycusis patients and 220 control subjects were enrolled in the study after examination by the otolaryngologist and audiology tests. Variations in the mtDNA control region were investigated by polymerase chain reaction and Sanger sequencing.ResultsA total of 113 sequence variants were observed in mtDNA, and variants were detected in 100% of patients, with 84% located in hypervariable regions. The frequencies of the variants, 16,223 C>T, 16,311 T>C, 16,249 T>C, and 15,954 A>C, were significantly different between presbycusis and control subjects.ConclusionThe statistically significant difference in the frequencies of four nucleotide variants in the mtDNA control region of presbycusis patients and controls is in agreement with previous experimental evidence and supports the role of mitochondria in the intracellular mechanism underlying presbycusis development. Moreover, these variants have potential as diagnostic markers for individuals at a high risk of developing presbycusis. The data also suggest the possible presence of changes in the mtDNA control region in presbycusis, which could alter regulatory factor binding sites and influence mtDNA gene expression and copy number.

| S-EPMC5344408 | biostudies-literature

Organization and variation of the Tetraonidae (Aves: Galliformes) mitochondrial DNA control region.

Project description:The mitochondrial DNA control region is the most polymorphic region of the mitochondrial genome. To infer the organization and variation of Tetraonidae mitochondrial DNA control region, the entire control region sequences of 18 species were analyzed. The length of the control region sequences ranged from 1127 bp (Bonasa sewerzowi) to 1156 bp (Centrocercus minimus). The average genetic distances among the species within the genera varied from 0.53% (Tympanuchus) to 9.42% (Bonasa). The average genetic distances showed insignificantly negative correlation with ts/tv. Five conserved sequence boxes in the domain II of Tetraonidae sequences were identified. The alignment of the Tetraonidae five boxes and CSB-1 sequences showed a few sequence variations. The results indicated that the genus Dendragapus might not be monophyletic.

| S-EPMC7800250 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data