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Scientists Decode Rat Genome - 2004-04-01

An international group of scientists has deciphered nearly the entire genetic blueprint for the rat. Since this rodent is commonly used in laboratory studies, the development is expected to stimulate progress in medicine.

Humanity has mixed emotions about the rat. Western cultures condemn it as a disease-bearing rodent unwelcome in the backyard. But Asians revere the rat as a creative problem solver and a hyperactive worker. The rat is the first sign of the Chinese zodiac.

If you ask a medical researcher about this animal, you would probably get a similarly positive response, like this one. "While we revile the rats as carriers of pestilence, they are also among nature's most resourceful and adaptive creatures and one of our close relatives," says Francis Collins, head of the U.S. government's Human Genome Institute, which helped fund the project to decode rat genes.

"Rats are a prominent model for studying normal physiology," he says. "Over the past two centuries, they have, in fact, saved countless human lives by the ways in which they serve as models for medical research and drug development."

Rats hold this position in medicine because they share the same general biological structure and functions common to all mammals. Therefore, studying diseases and testing drugs in rats helps scientists understand their implications for humans.

In fact, rats and people have about 90 percent of the same genes, the molecules of DNA in cells that control physical function. Furthermore, almost all human disease genes have rat counterparts. Therefore, a genetic map of the rat has been a major scientific goal, as was the mouse genetic map published in 2002. Now, 90 percent of the rat genome has been deciphered by an international team led by the Baylor College of Medicine in Houston, Texas and published in the journal Nature.

The University of Wisconsin scientist who co-authored the Nature paper, Howard Jacob, says the development will make it easier to design rats that can mimic specific human diseases. He notes that this will reduce the time and expense needed to understand the biology of the ailments and search for cures.

"Rats remain the dominant preclinical model of human disease for developing new drugs. Better rat models would decrease drug failures in clinical trials, which would decrease development costs and time to market," says Mr. Jacobs. "For the first time, rat models can be built that incorporate the clinical and genetic similarities to the human disease."

The rat is the third mammal to have its genes decoded, after those of people and mice. The researchers say having the two rodent gene maps is useful because if there are similarities between them, there is a greater chance humans will share the traits.

Three-way comparisons can help resolve details of how mammals evolved. For example, Baylor College of Medicine researcher Richard Gibbs says genes shared by mice and rats, but not people, represent evolutionary changes after humans and rodents split from a common ancestor many millions of years ago.

"Other break points actually occur in the rat and not in the mouse. Therefore, this has occurred since the divergence of the two species," says Mr. Gibbs. "So that shows you how you can get this kind of timing now from a third species that you could not get from two and how you now may infer these full evolutionary trees."

If three mammal genomes are good, then more are presumably better. Francis Collins foresees genetic maps of 20 other mammals coming forth in the next three years. He says that using other animals for comparison is turning out to be one of the most compelling ways to understand how human genes work.

"So while today may be the day of the rat, tomorrow may bring the publications on the chimp, the chicken, the dog, and a long list of others that you can anticipate will greatly illuminate human biology and lead us to advances in human medicine," he says.