A team of researchers from Johns Hopkins University School of Medicine, Baltimore, report that they have developed a second-generation "lab on a silicon chip" that, for the first time, rapidly and reliably sequences all mitochondrial DNA, according to an article in the September issue of the Journal of Molecular Diagnostics.
Mitochondria, the energy-producing organelles that power human cells, are unique because they are equipped with their own genetic instructions distinct from the DNA stored in the cell nucleus.
The researchers say their full-sequence chip, called the "MitoChip v2.0," will be a key tool in accelerating research on mitochondrial DNA, a growing area of scientific interest. This interest stems from data that suggest that natural sequence variations and/or mutations in each person’s mitochondrial DNA could be biologically informative in fields as diverse as cancer diagnostics, gerontology and criminal forensics.
According to Joseph Califano, MD, a scientist at Johns Hopkins and the report’s senior author, the MitoChip v2.0 demonstrated better sensitivity than its predecessor to sequence variations in head and neck cancer samples. The v2.0 also detected nearly three dozen variations in the noncoding D-loop, long considered to be a sequencing "no-man’s land."
"The real interesting thing is nobody has been able to study these D-loop alterations very well," said Dr. Califano. "They clearly occur in tumor cells, and there is some type of selection process for them. But their functional significance has been hard to know. Now, you can sequence the D loop so readily and begin to look harder for associations in certain cancers."
"With mitochondrial DNA, there is a mass advantage," added Anirban Maitra, MD, one of the report’s authors. "Whereas nuclear DNA contains just two copies of every gene, there are literally hundreds of mitochondria in most cells. If you are screening saliva or other bodily fluids with a limited number of cells to analyze, mitochondrial DNA gives you more to work with and a better chance of detecting mutations that might be associated with a developing cancer."
Dr. Califano’s research is supported by the National Institute of Dental and Craniofacial Research and Dr. Maitra’s research is supported by the National Cancer Institute.
