scholarly journals Decreased mitochondrial D-loop region methylation mediates an increase in mitochondrial DNA copy number in CADASIL

2022 ◽  
Vol 14 (1) ◽  
Author(s):  
Jiewen Zhang ◽  
Junkui Shang ◽  
Fengyu Wang ◽  
Xuejing Huo ◽  
Ruihua Sun ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Copy Number ◽  
Control Group ◽  
Compensatory Mechanism ◽  
Dna Copy Number ◽  
Gender Stratification ◽  
Loop Region ◽  
Mitochondrial Dna Copy Number ◽  
D Loop

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a typical neurodegenerative disease associated with mitochondrial dysfunction. Methylation of the D-loop region and mitochondrial DNA copy number (mtDNAcn) play a critical role in the maintenance of mitochondrial function. However, the association between D-loop region methylation, mtDNAcn and CADASIL remains unclear. Methods Overall, 162 individuals were recruited, including 66 CADASIL patients and 96 age- and sex-matched controls. After extracting genomic DNA from the peripheral white blood cells, levels of D-loop methylation and mtDNAcn were assessed using MethylTarget sequencing and real-time PCR, respectively. Results We observed increased mtDNAcn and decreased D-loop methylation levels in CADASIL patients compared to the control group, regardless of gender stratification. Besides, we found a negative correlation between D-loop methylation levels and mtDNAcn. Mediation effect analysis shows that the proportion of the association between mtDNAcn and CADASIL that is mediated by D-loop methylation is 11.6% (95% CI 5.6, 22.6). After gender stratification, the proportions of such associations that are mediated by D-loop methylation in males and females were 7.2% (95% CI 2.4, 19.8) and 22.0% (95% CI 7.4, 50.1), respectively. Conclusion Decreased methylation of the D-loop region mediates increased mtDNAcn in CADASIL, which may be caused by a compensatory mechanism of mitochondrial dysfunction in patients with CADASIL.

Mitochondrial DNA copy number and D-loop region methylation in carriers of amyotrophic lateral sclerosis gene mutations

Epigenomics ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1431-1443 ◽  
Author(s):  
Andrea Stoccoro ◽  
Lorena Mosca ◽  
Vittoria Carnicelli ◽  
Ugo Cavallari ◽  
Christian Lunetta ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Gene Mutations ◽  
Dna Copy Number ◽  
Loop Region ◽  
Mitochondrial Dna Copy Number ◽  
D Loop ◽  
Lateral Sclerosis

Rare instances of non-random dropout with the monochrome multiplex qPCR assay for mitochondrial DNA copy number

2021 ◽  
Author(s):  
Stephanie Y Yang ◽  
Charles E Newcomb ◽  
Stephanie L Battle ◽  
Anthony YY Hsieh ◽  
Hailey L Chapman ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Dna Copy Number ◽  
Loop Primer ◽  
Mitochondrial Dna Copy Number ◽  
D Loop

Mitochondrial DNA copy number (mtDNA-CN) is a proxy for mitochondrial function and has been of increasing interest to the mitochondrial research community. There are several ways to measure mtDNA-CN, ranging from whole genome sequencing to qPCR. A recent article from the Journal of Molecular Diagnostics described a novel method for measuring mtDNA-CN that is both inexpensive and reproducible. However, we show that certain individuals, particularly those with very low qPCR mtDNA measurements, show poor concordance between qPCR and whole genome sequencing measurements. After examining whole genome sequencing data, this seems to be due to polymorphisms within the D-loop primer region. Non-concordant mtDNA-CN was observed in all instances of polymorphisms at certain positions in the D-loop primer regions, however, not all positions are susceptible to this effect. In particular, these polymorphisms appear disproportionately in individuals with the L, T, and U mitochondrial haplogroups, indicating non-random dropout.

scholarly journals Mitochondrial DNA methylation and copy number predict body composition in a young female population

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Laura Bordoni ◽  
Vanessa Smerilli ◽  
Cinzia Nasuti ◽  
Rosita Gabbianelli
Keyword(s):  
Dna Methylation ◽  
Body Composition ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Buccal Swab ◽  
Dna Copy Number ◽  
Female Population ◽  
Mitochondrial Dna Copy Number ◽  
Buccal Swabs ◽  
D Loop

Abstract Background Since both genomic and environmental factors are involved in obesity etiology, several studies about the influence of adiposity on both nuclear DNA and mitochondrial DNA methylation patterns have been carried out. Nevertheless, few evidences exploring the usage of buccal swab samples to study mitochondrial DNA epigenetics can be found in literature. Methods In this study, mitochondrial DNA from buccal swabs collected from a young Caucasian population (n = 69) have been used to examine potential correlation between mitochondrial DNA copy number and methylation with body composition (BMI, WHtR and bioimpedance measurements). Results A negative correlation between mitochondrial DNA copy number and BMI was measured in females (p = 0.028), but not in males. The mean percentage of D-loop methylation is significantly higher in overweight than in lean female subjects (p = 0.003), and a specific CpG located in the D-loop shows per se an association with impaired body composition (p = 0.004). Body composition impairment is predicted by a combined variable including mtDNA copy number and the D-loop methylation (AUC = 0.785; p = 0.009). Conclusions This study corroborates the hypothesis that mitochondrial DNA carries relevant information about body composition. However, wider investigations able to validate the usage of mtDNA methylation from buccal swabs as a biomarker are warranted.

Mitochondrial DNA Copy Number in Peripheral Blood in the First Trimester of Pregnancy and Different Preeclampsia Clinical Phenotypes Development: A Pilot Study

2018 ◽  
Vol 26 (8) ◽  
pp. 1054-1061 ◽  
Author(s):  
Andrea Busnelli ◽  
Debora Lattuada ◽  
Stefania Ferrari ◽  
Marco Reschini ◽  
Barbara Colciaghi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Peripheral Blood ◽  
Copy Number ◽  
First Trimester ◽  
Control Group ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
First Trimester Of Pregnancy ◽  
And Oxidative Stress

Inflammation and oxidative stress are intrinsically linked to early poor placentation, typical of pregnancies complicated by preeclampsia associated with intrauterine growth restriction (PE-IUGR). Low mitochondrial DNA copy number (mtDNAcn) in peripheral blood constitutes a good peripheral surrogate marker of inflammation and oxidative stress. On these basis, we explored a possible correlation between mtDNAcn in peripheral blood in the first trimester of pregnancy and the PE-IUGR onset. To shed light on this issue, we setup a nested case–control study from a prospective cohort of pregnant women undergoing first-trimester aneuploidies screening. Two groups of patients affected by PE classified according to the clinical phenotype were identified: (1) patients who developed PE-IUGR and (2) patients who developed PE associated with appropriate for gestational age intrauterine fetal growth (PE-AGAf). Controls were women with a physiologic pregnancy matched to cases on the basis of age (±6 months, ratio 2:1). Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction and normalized to nuclear DNA. The median (interquartile range) mtDNAcn in peripheral blood in patients with PE-IUGR (n = 12) and in patients with PE-AGAf (n = 16) was 70 (44-97) and 108 (95-145), respectively ( P = .004). Both these values were significantly lower than that detected in the control group (161[133-183], P < .001). The area under the receiver–operator curve for PE-IUGR and PE-AGAf were 0.94 (95% confidence interval [CI]: 0.88-1.00, P < .001) and 0.81 (95%CI: 0.70-0.91, P < .001), respectively. In conclusion, MtDNAcn in peripheral blood resulted significantly lower both in patients affected by PE-IUGR and in those affected by PE-AGAf when compared to controls. The accuracy of this biomarker resulted particularly good in predicting PE-IUGR.

Hypomethylation of mitochondrial D-loop and ND6 with increased mitochondrial DNA copy number in the arsenic-exposed population

Toxicology ◽  
2018 ◽  
Vol 408 ◽  
pp. 54-61 ◽  
Author(s):  
Tamalika Sanyal ◽  
Pritha Bhattacharjee ◽  
Sandip Bhattacharjee ◽  
Pritha Bhattacharjee
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Exposed Population ◽  
D Loop

scholarly journals Telomere Length but Not Mitochondrial DNA Copy Number Is Altered in Both Young and Old COPD

2021 ◽  
Vol 8 ◽  
Author(s):  
Sandra Casas-Recasens ◽  
Nuria Mendoza ◽  
Alejandra López-Giraldo ◽  
Tamara Garcia ◽  
Borja G. Cosio ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Lung Function ◽  
Mitochondrial Dysfunction ◽  
Telomere Length ◽  
Copy Number ◽  
Accelerated Ageing ◽  
Dna Copy Number ◽  
Old Patients ◽  
Mitochondrial Dna Copy Number ◽  
Severe Copd

Accelerated ageing is implicated in the pathogenesis of respiratory diseases as chronic obstructive pulmonary disease (COPD), but recent evidence indicates that the COPD can have roots early in life. Here we hypothesise that the accelerated ageing markers might have a role in the pathobiology of young COPD. The objective of this study was to compare two hallmarks of ageing, telomere length (TL), and mitochondrial DNA copy number (mtDNA-CN, as a surrogate marker of mitochondrial dysfunction) in young (≤ 50 years) and old (&gt;50 years) smokers, with and without COPD. Both, TL and mtDNA-CN were measured in whole blood DNA by quantitative PCR [qPCR] in: (1) young ever smokers with (n = 81) or without (n = 166) COPD; and (2) old ever smokers with (n = 159) or without (n = 29) COPD. A multivariable linear regression was used to assess the association of TL and mtDNA-CN with lung function. We observed that in the entire study population, TL and mtDNA-CN decreased with age, and the former but not the latter related to FEV1/FVC (%), FEV1 (% ref.), and DLCO (% ref.). The short telomeres were found both in the young and old patients with severe COPD (FEV1 &lt;50% ref.). In addition, we found that TL and mtDNA-CN were significantly correlated, but their relationship was positive in younger while negative in the older patients with COPD, suggesting a mitochondrial dysfunction. We conclude that TL, but not mtDNA-CN, is associated with the lung function impairment. Both young and old patients with severe COPD have evidence of accelerated ageing (shorter TL) but differ in the direction of the correlation between TL and mtDNA-CN in relation to age.

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