Related Experiment Video
Updated: Jul 4, 2026
09:15
Measuring Single-Cell Mitochondrial DNA Copy Number and Heteroplasmy Using Digital Droplet Polymerase Chain Reaction
Published on: July 12, 2022
Variations in mitochondrial DNA copy numbers in MS brains
Andrei Blokhin1, Tamara Vyshkina, Samuel Komoly
1VA Medical Center, 800 Irving Avenue, Syracuse, NY 13210, USA.
Journal of Molecular Neuroscience : MN
|June 21, 2008
Summary
Multiple sclerosis (MS) brain studies reveal normal mitochondrial DNA (mtDNA) copy numbers in plaques but higher levels in normal-appearing gray matter (NAGM) neurons. An age-related decline in mtDNA copy number was observed in both MS patients and controls.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Genetics
Background:
- Mitochondrial dysfunction is implicated in neurodegenerative diseases like multiple sclerosis (MS).
- Previous research excluded MS pathology-related increases in deleted mtDNA molecules.
- This study investigates mitochondrial DNA (mtDNA) copy number variations in MS brain tissue.
Purpose of the Study:
- To determine pathology-related variations in mtDNA copy numbers in the brains of multiple sclerosis patients.
- To explore the relationship between mtDNA copy number, brain region, pathology, and age in MS.
- To understand the role of mitochondria in neurodegeneration associated with inflammatory demyelination.
Main Methods:
- Quantified mtDNA copy number variations (ND1/r18S) using real-time PCR.
- Analyzed laser-dissected neurons and glial cells from postmortem MS and control brain tissues (NAGM, NAWM, plaques, GM, WM).
- Correlated mtDNA copy number values with tissue regions, pathology, and age.
Main Results:
- mtDNA copy numbers were similar in MS white matter (NAWM) and plaques compared to controls.
- Significantly higher mtDNA copy numbers were found in neurons of normal-appearing gray matter (NAGM) in MS patients.
- NAGM neurons exhibited higher mtDNA copy numbers than gray matter (GM) in non-neurological disease (NND) controls.
- An age-related decline in mtDNA copy number was observed in neurons of both MS patients and NND controls.
Conclusions:
- mtDNA copy number variations do not change in MS plaques.
- Higher mtDNA copy numbers in NAGM suggest compensatory replication of mitochondria in the cortex.
- The age-related decline in mtDNA copy number may contribute to late-onset MS.
- Mitochondrial contributions to tissue degeneration in MS warrant further investigation.
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
02:59Animal Mitochondrial Genetics
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:29Non-nuclear Inheritance
Most DNA resides in the nucleus of a cell. However, some organelles in the cell cytoplasm—such as chloroplasts and mitochondria—also have their own DNA. These organelles replicate their DNA independently of the nuclear DNA of the cell in which they reside. Non-nuclear inheritance describes the inheritance of genes from structures other than the nucleus.