Let Us Praise the Lowly Rat

Detest them if you will, but now that scientists have decoded 90 percent of the genome of the rat, that hardy rodent may one day save your life. By Kristen Philipkoski.

Scientists have deciphered virtually all the genome of the rat, an animal considered loathsome by almost everyone except a researcher.

Science has prized the lowly rat for more than 150 years, as a model for studying human disease. That value increases exponentially now that the animal's DNA sequence is known.

While the mouse, whether it likes it or not, is king of the research lab, the rat is unique for several reasons. It can exhibit heart disease, diabetes and various neurological disorders, making it a good test model for drugs that might fight those problems. The mouse can't do that. Also, the rat is the third mammal sequenced, giving researchers an opportunity to compare all three and make more accurate measurements of genes associated with both disease and evolution.

"Sequencing the rat genome represents much more than an odometer moment," said Francis Collins, director of the Human Genome Research Institute, during a press conference on Wednesday in Washington, D.C. "It gives the opportunity for triangular comparison -- three is vastly better than two."

"If you have two points, you can't really determine the distance between them, but if you have three, you can using trigonometry," said Richard Gibbs, director of the genome sequencing program at Baylor College of Medicine in Houston, who coordinated the rat genome project.

A consortium of scientists from 13 institutes around the world contributed to the project and published their data in the April 1 issue of the journal Nature. They chose to publish the 90 percent of the genome that was complete, instead of waiting until they had completed the entire genome. The remaining 10 percent represents the most difficult regions of the genome to decode and alone will take about one-third the time and cost of the entire project. The project took several years and cost about $110 million.

"It was a cost-benefit decision" to release the 90 percent that was complete so other researchers could start using in now, Gibbs said.

They found most of the rat's genes have a counterpart in humans, Gibbs said. The genome is slightly larger than the mouse and slightly smaller than the human. All three have a similar number of genes -- probably between 25,000 and 30,000.

Studies on the rat genome have already led to significant discoveries, said Howard Jacob, a senior author on the paper and researcher at the Medical College of Wisconsin. For example, scientists had been unable to find the gene that caused polycystic kidney disease by using patient samples. Researchers mapped a region of the rat's genome where they suspected the gene was located and noticed the same sequence of letters (A, C, T and G, which represent the nucleotides that make up all DNA: adenine, cytosine, thymine and guanine). By lining up these two sections of DNA, they were able to pinpoint the human gene responsible for polycystic kidney disease.

Now researchers can build even more accurate rat models for human disease, Jacob said. Until now, researchers used rats to test drugs based on the symptoms they displayed. Now, they can also know if the rat has regions of its genome associated with a particular disease in common with humans.

In addition to the Nature study, the consortium will publish and additional 30 papers on the rat genome in the journal Genome Research.