K.C. researchers get patent for innovative DNA probes

? A husband-and-wife research team at Children’s Mercy Hospital in Kansas City has pulled off the genetic equivalent of finding a needle in a haystack.

By developing groundbreaking refinements to lab tools called DNA probes, geneticists Joan Knoll and Peter Rogan can pinpoint abnormalities even within a single gene.

That is far greater precision than was possible before with such probes.

The probes could make it much easier for doctors to decide which chemotherapy drugs to prescribe to cancer patients, what kind of rehabilitation to offer developmentally disabled children or what advice to give families with a history of genetic disorders.

“We have the means to very precisely probe chromosome abnormalities,” Rogan said. “We have enormous confidence that the probe we make is capable of making the distinctions.”

Rogan and Knoll were granted a patent last week on their DNA probe technology. The researchers already have devised about 400 probes for about 100 genetic diseases.

Their next step is to make the probes easier for lab technicians to analyze. Within a few years, they hope to be manufacturing probes doctors can use to diagnose literally hundreds of disorders.

“It’s incredibly exciting that we can define things at a smaller and smaller scale, and home in on single genes,” said Daynna Wolff, a geneticist at the Medical University of South Carolina who is familiar with Rogan and Knoll’s work.

Genetic disorders number in the thousands. They include such relatively well-known conditions as sickle-cell disease, cystic fibrosis and Down syndrome, as well as a host of rare disorders.

Treatment of these conditions can vary greatly depending upon a patient’s genetic makeup. Family-planning decisions also can hinge on a parent’s genetic background. Those are the kinds of situations where Rogan and Knoll expect doctors to put their DNA probes to use.

“This is the real power of genetics, to marshal the power of predictive medicine,” Rogan said. “Even if you look at something as common as Down syndrome, there is so much variation. Being able to know what specialists they need to see and when is valuable.”

DNA probes have been available commercially for about 10 years. While they may employ different technologies, they all work this way:

Imagine the double helix of a DNA molecule as a kind of zipper. Each half of the DNA zipper has a long row of molecular teeth, called nucleotides, that link with certain nucleotides on the other half.

DNA has four kinds of nucleotides, and the order in which they appear along the DNA zipper forms the code for regulating what happens in the cells of our bodies.

DNA probes can pinpoint where certain teeth appear on the DNA zipper. If a tooth is missing or is in the wrong place, it can indicate a genetic disorder.

The probes are manufactured in a laboratory to contain a small section from each half of the DNA zipper. When a probe is mixed with a patient’s DNA in the laboratory, its teeth link with the other half of the zipper. Under a microscope, the probes appear as colored dots, so researchers can see whether they’re in the right place.

Commercially produced DNA probes examine large sections of DNA, as many as several hundred thousand nucleotides. That is fine for discovering many genetic disorders. But some of these disorders have small variations that commercial probes are too large to detect.

Knoll and Rogan’s probes contain just 1,200 to 5,000 nucleotides. That should allow doctors to fine-tune their diagnoses.

Knoll and Rogan plan to license their probe technology broadly. They also are working on a business of their own that could include an online catalog of made-to-order DNA probes. A year from now, they could be ready to provide probes to researchers. A few years after that, they could have probes for doctors to use to diagnose patients.

“There are simply some patients who can’t be diagnosed with the existing probes on the market,” Rogan said.