Scientists Develop New Way to Detect Mutations

In Brief

Researchers at Harvard Medical School reported last Wednesday the discovery of a faster, more specific technique to locate defective genes linked to diseases such as cystic fibrosis and cancer.

Professor of Pathology Dr. Jeffrey L. Sklar and co-workers have used enzymes called resolvases, isolated from bacteriainfecting viruses, to hunt for mutations in large genes. The technique, reported in the journal Nature Genetics, has proved capable of detecting 94 percent of mutations in a gene.

"We have established the use of these kinds of techniques, using a new approach," said Dr. Robert D. Mashal, instructor of medicine at the Medical School and first author on the study. "It is preliminary, but others are now hot on our trial trying to find better enzymes that function in a similar way."

Two common types of techniques now used to detect genetic mutations are sequencing, which is labor-intensive and slow, and methods using gels, which can only detect the presence of a genetic mutation and not its location.

A third approach, called chemical mismatch cleavage, is as accurate as the resolvase method but is not widely used because it requires chemicals which are either explosive or mutagenic.


Resolvases cleave DNA at sites where bases are mismatched, said Dr. Michael Dean, chief of the human genetic section of the National Cancer Institute in Frederick, Maryland.

"This is an exciting new step, giving us a new avenue for looking at the gene," said Dean, who wrote an accompanying commentary in the journal on the group's work.

The resolvases tested can be as much as 100 times more specific than gel techniques at locating mutations, Mashal said, but the genes still have to be sequenced after they are identified as mutants.

"[Resolvases] are a way to find where the mutations are in a big, huge gene so we only have to sequence part [of the gene]," Mashal said.

Clinically, the technique can be used to let patients know whether or not they are predisposed to breast cancer and other hereditary disorders. But Mashal said the method is not 100 percent accurate, as most patients would prefer.

Knowing the location of defective genes may also allow scientists to replace them with healthy ones, Mashal said.