U. chemistry professors Cynthia Burrows and Henry White led research team that developed a new way to detect DNA damage by adapting so-called nanopore technology used to sequence DNA and decipher genetic blueprints. Photo Credit: Lee J. Siegel, University of Utah

Research Study uses a protein known as a nanopore to pinpoint missing pieces in genome.

University of Utah chemists are refining a method for combing a persons genome in search of DNA damage that leads to mutations and disease. Professors Henry White and Cythnia Burrows are building on the so-called nanopore technique of sequencing DNA in which strands of genetic material are passed through a molecule-sized path, a protein known as a "nanopore."

"My interest in not just sequencing the A, T, C and G [letters corresponding to the basic molecules of DNA] but changes that happen on those bases from mutations," said Burrows. "A certain amount is OK because it gets fixed. That damage is ultimately where disease is caused, especially age-related diseases like cancer."

White, who chairs the U. chemistry department, and Burrows describe their method in a string of recent studies, including one published this week in the prestigious Proceedings of the National Academy of Sciences.

Strands of DNA are made of "nucleotide bases," the building blocks of nucleic acids. Some stretches of DNA strands are genes, which serve as codes that are translated into proteins.

The new mutation-hunting method looks for places where a base is missing known as an "abasic site" one of the most frequent lesions in the 3 billion-letter human genome. Such DNA damage happens 18,000 times a day in a typical human cell from exposure to countless irritants, such as sunlight, car exhaust and fast food.

"Over the course of a lifetime not every piece of damage gets repaired. You accumulate those over a lifetime. At some point you have a higher likelihood of one of these disease-causing mutations cropping up," Burrows said. Besides various cancers, other diseases arising from DNA damage include Huntingtons and atherosclerosis.

The cost of sequencing a persons genome will soon drop to less than $1,000 and become commonplace, allowing patients greater access to their genetic predisposition to disease and responsiveness to particular treatments. It currently costs about $10,000 and takes at least a week.

Burrow and Whites team adapted the nanopore sequencing technique so that it locates damage with the help of electrically charged saline-like liquids. Their method measures changes in the electrical signal as the DNA passes through the nanopore, like thread passing through the eye of a needle.

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University of Utah chemists developing new way to identify DNA damage