Bringing bold color to chromosomes.

When television executives colorize classic black-and-white films such as Casablanca, howls of protest from movie purists fill the air. In contrast, a report announcing the colorization of human chromosomes has raised a hue and cry of delight among geneticists-24 hues, in fact.

By attaching fluorescent markers to carefully chosen DNA sequences, investigators have learned how to paint a color-coded picture of all 24 human chromosomes (the sex chromosomes X and Y and the 22 chromosomes present in pairs).

This newly developed artistic ability should improve diagnosis of the many chromosomal abnormalities that cause cancer or other genetic diseases.

"It offers the promise of greatly improving the efficiency, as well as potentially the accuracy, of both clinical and research chromosome analysis," says Huntington F. Willard of Case Western Reserve University School of Medicine in Cleveland.

The color-coding technique is described in the April Nature Genetics by Michael R. Speicher, Stephen Gwyn Ballard, and David C. Ward of Yale University School of Medicine. It is "a beautiful (scientifically and literally) study," observes Michelle M. Le Beau of the University of Chicago in an accompanying commentary.

Researchers studying chromosomes traditionally stain them to reveal distinctive black-and-white banding patterns. By painstakingly analyzing the bands, a task difficult to automate, scientists can often spot chromosomal irregularities.

To improve the odds of finding abnormalities, and to make possible the automation of such analysis, researchers have experimented with linking fluorescent markers to known DNA sequences. These DNA-based probes attach only to specific sites within the human chromosomes.

By labeling thousands of chromosome-specific DNA sequences with five different fluorescent markers, the Yale group was able to produce unique spectral fingerprints for each of the 24 chromosomes. Using these fingerprints, they assigned a different color to the computer image of each chromosome.

This method has made it easier for researchers to detect abnormalities such as translocations, in which pieces of chromosomes exchange places with one another. "That's very important for tumor cytogenetics. Many of these rearrangements can't normally be deciphered," says Speicher.

Other research groups are working on variations of the Yale technique, ones they hope will be less costly or even easier to automate.