UNC-CH Chemists Develop Better Gene Mutation Detection Method

Those alternations, called single nucleotide polymorphisms, occur when one chemical component of the genetic code is changed in some way by additions, deletions or relocations of genetic material, the scientists say. Knowing what and where those changes are is critical to finding and designing drugs that can act on them specifically without interfering with the activity of healthy genes.

Potentially, the new method could allow scientists to screen for minute changes in the genetic makeup of humans, animals, plants or viruses, UNC-CH's Dr. Holden Thorp said. Comparable techniques already available for screening genes are confined to research laboratories, are labor intensive and are therefore slow and expensive.

Dr. Patricia A Ropp, postdoctoral research associate in pharmacology at the UNC-CH School of Medicine, and Thorp, professor of chemistry, have been developing the new method. In a paper published in the September issue of the journal Chemistry and Biology, the two describe it.

"Our method uses inexpensive electronic equipment without cumbersome procedures," Thorp said. "It is based on the measurement of different but very small electrical currents generated when guanine is paired with its correct DNA chemical partner versus an incorrect chemical partner."

The incorrect chemical is a single nucleotide polymorphism mutation or SNP, he said. With the new technique, he and Ropp can detect specific mutations associated with specific diseases.

"As we can continue to make these kinds of advances, we'll eventually have a device that can be used to do these analyses routinely so that they will impact people's everyday lives," Thorp said. "It's very exciting."

The genetic code -- or proper order of smaller base elements making up the massive DNA molecule -- consists of the nucleotide "building blocks" adenine, thymine, guanine and cytosine, which are abbreviated A, T, G and C, respectively, he said. Pairs of the chemicals, either A-T or G-C, line up in the DNA molecule, models of which look something like long, twisted ladders.

The National Science Foundation supported the research along with Xanthon Inc., a new company in Research Triangle Park, N.C. that has licensed rights to the invention from the university.

Xanthon's early products will be introduced in late 2000 and will use the new approach to analyze gene expression in whole cells, said Thorp.

The chemist founded Xanthon in 1996 with Jim Skinner and Carson Loomis. The company is financed by local investors, including Intersouth Partners, Franklin Street/Fairview Capital, The Aurora Funds, Centennial Ventures and the N.C. Technology Development Authority. Noro-Moseley Partners and Cordova Ventures of Atlanta also recently began funding the company.