Emerging methods for and novel insights gained by absolute quantification of mitochondrial DNA copy number and its clinical applications

2021 ◽  
pp. 107995
Author(s):  
Brian Li ◽  
Pola Kalinowski ◽  
BaRun Kim ◽  
Andrew Pauls ◽  
Damon Poburko
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Absolute Quantification ◽  
Clinical Applications ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

scholarly journals Telomere Shortening linked to Disability and Mitochondrial DNA Copy Number in Patients with Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Author(s):  
José Alfonso Cruz-Ramos ◽  
Gabriela del Carmen López-Armas ◽  
Eduardo Ignacio Díaz-Barba ◽  
Mónica Navarro-Meza ◽  
Miguel Ángel Macías-Islas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Binary Logistic Regression ◽  
Peripheral Blood Leukocyte ◽  
Absolute Quantification ◽  
Severe Disability ◽  
Dna Copy Number ◽  
Binary Logistic Regression Model ◽  
Mitochondrial Dna Copy Number

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of disability and neurological damage. The present work evaluated LTL and mtDNA-CN in 75 relapsing-remittent MS (RRMS) patients 50 of whom had an Expanded Disability Status Scale (EDSS) 0 to 3 (mild-moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). Absolute LTL and absolute mtDNA-CN were measured via real-time polymerase chain reaction (qPCR). The LTL and mtDNA-CN were significantly lower in RRMS severe disability than in RRMS mild-moderate disability (3.924 ± 0.124 vs 2.854 ± 0.092, p<00001; 75.14 ± 1.77 vs 68.06 ± 1.608, p<0.00001, respectively). The LTL and mtDNA-CN showed a linear correlation in RRMS with mild-moderate disability (r=0.2986, p=0.0351). In addition, in a binary logistic regression model the LTL can predict severe disability (AUC=0.697, p=0.0031, cutoff ≤ 3.0875 Kb, sensitivity= 73.1%, specificity=62.5%), the prediction is improved by including age to the model (AUC=0.765, <0.0001, sensitivity=78.26%, specificity=81.25%). Aging is closely linked to the development of disability in RRMS and can be evaluated through LTL and mtDNA-CN absolute quantification.

scholarly journals Telomere Shortening linked to Disability and Mitochondrial DNA Copy Number in Patients with Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Author(s):  
José Alfonso Cruz-Ramos ◽  
Gabriela del Carmen López-Armas ◽  
Eduardo Ignacio Díaz-Barba ◽  
Mónica Navarro-Meza ◽  
Miguel Ángel Macías-Islas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Binary Logistic Regression ◽  
Peripheral Blood Leukocyte ◽  
Absolute Quantification ◽  
Severe Disability ◽  
Dna Copy Number ◽  
Binary Logistic Regression Model ◽  
Mitochondrial Dna Copy Number

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of disability and neurological damage. The present work evaluated LTL and mtDNA-CN in 75 relapsing-remittent MS (RRMS) patients 50 of whom had an Expanded Disability Status Scale (EDSS) 0 to 3 (mild-moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). Absolute LTL and absolute mtDNA-CN were measured via real-time polymerase chain reaction (qPCR). The LTL and mtDNA-CN were significantly lower in RRMS severe disability than in RRMS mild-moderate disability (3.924 ± 0.124 vs 2.854 ± 0.092, p<00001; 75.14 ± 1.77 vs 68.06 ± 1.608, p<0.00001, respectively). The LTL and mtDNA-CN showed a linear correlation in RRMS with mild-moderate disability (r=0.2986, p=0.0351). In addition, in a binary logistic regression model the LTL can predict severe disability (AUC=0.697, p=0.0031, cutoff ≤ 3.0875 Kb, sensitivity= 73.1%, specificity=62.5%), the prediction is improved by including age to the model (AUC=0.765, <0.0001, sensitivity=78.26%, specificity=81.25%). Aging is closely linked to the development of disability in RRMS and can be evaluated through LTL and mtDNA-CN absolute quantification.

Abstract 751: Lung mitochondrial DNA copy number variations: E-cig users, smokers, and never-smokers

2021 ◽  
Author(s):  
Kellie M. Mori ◽  
Joseph P. McElroy ◽  
Daniel Y. Weng ◽  
Sangwoon Chung ◽  
Sarah A. Reisinger ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number ◽  
Copy Number Variations ◽  
Dna Copy Number ◽  
Dna Copy Number Variations ◽  
Mitochondrial Dna Copy Number ◽  
Never Smokers

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.

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