they have developed a second generation “lab on a silicon chip” called the MitoChip v2.0 that for the first time rapidly and reliably sequences all mitochondrial DNA. Mitochondria, the energy-producing organelles that power our cells, are unique because they are equipped with their own genetic instructions distinct from the DNA stored in the cell nucleus. The Mitochip v2.0 full-sequence chip will be a key tool in accelerating research on mitochondrial DNA, a growing area of scientific interest. This interest stems from data that suggests 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.
Data suggests 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. Hundreds to thousands of mitochondria exist in each human cell, occupying up to a quarter of their cytoplasm. Sometimes informally described as “cellular power plants,” mitochondria convert organic materials into ATP, the cell’s energy currency and without which life would cease.
Dr. Maitra said that despite the original Mitochip’s 96 percent success rate assigning base calls, there was room for improvement. Led by Drs. Shaoyu Zhou and Keyaunoosh Kassauei, the Hopkins group cobbled together the MitoChip v2.0. reported in this month’s Journal of Molecular Diagnostics. It yielded essentially the same base-call success rate as its predecessor, showed near perfect reproducibility in replicate experiments, and detected more variations than the first-generation chip.
As a proof of principle, the Mitochip v2.0 also detected 31 variations in the non-coding D-loop of 14 head and neck tumor samples. Included in this tally were several mutations that possibly are informative of the disease.
“The real interesting thing is nobody has been able to study these D-loop alterations very well,” said 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.”
Using the chip they have arrayed 500 of the most common haplotypes – or grouped patterns of known DNA variations – banked in the mitochondrial public database.
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