Monday, Dec. 27, 1993

Genetic Geography

By Christine Gorman

The first maps of the New World, drawn back in the age of Columbus and Magellan, were pitifully primitive. The early European explorers and cartographers thought that America was just a narrow strip of land and that the Pacific Ocean was small enough for a galleon to cross in a couple of weeks. But despite all their shortcomings, those first stabs at mapmaking captured the imaginations of adventurers and spurred more voyages of discovery.

In much the same way, today's explorers of the genetic frontier have doggedly navigated the 23 pairs of human chromosomes in their search for various genes -- not always sure which landmarks to trust or how far away the goal was. The hunt will now be easier, thanks to last week's announcement that an international team of scientists, led by Dr. Daniel Cohen at the Center for the Study of Human Polymorphism in Paris, has produced the first full-fledged -- if still rough -- map of the human genome. "This is a major step forward," says David Ward, a Yale geneticist who has been analyzing the map for errors. "It's a first pass, and it will have its warts. But it's still significant."

Composed of long chains of DNA containing perhaps 100,000 genes, the human genome is far too vast to analyze all at once. So scientists use special enzymes to chop the chromosomes into small manageable pieces and pick out small identifiable stretches -- called markers -- on each segment. When researchers are searching for a disease gene, they look for a marker that is common to all people who suffer from that ailment. If one is found, then the defective gene is probably located somewhere near that marker. The problem is that although the gene hunters know where the marker is located on the chromosome, they don't necessarily know how close it lies to the suspect gene.

That's why Cohen's new map will come in handy. To produce it, his group sliced many sets of chromosomes into thousands of segments and put each piece into a yeast cell. The cells then made thousands of copies of every piece of the human DNA. By studying different possible arrangements, Cohen's computerized machines were able to figure out the positions of a whole list of common markers as well as the proper order of the pieces.

Cohen's laboratory now has in storage multiple copies, or clones, of about 33,000 chromosome segments. So if gene hunters want to search the area around a particular marker, they can request copies of the relevant DNA segments. Says Cohen: "You can call and say, 'I need this and this clone,' and you'll get it in two days."

Anyone wanting a description of the entire map should be able to obtain it through a computer: Cohen has promised to feed the information into the Internet, the global communications network most heavily used by scientists. "It should be equally available to all the world," he says.

The ultimate goal for biologists is to determine the exact sequence of all the chemical components of all 100,000 genes. That will give scientists the full, detailed genetic instructions for a human being. But since that map will contain 3.5 billion separate points, it probably won't be completed until after the turn of the century.

With reporting by J. Madeleine Nash/Chicago