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Scientists Have Genetic Blueprint of Mouse

Effort seen aiding search for human therapies

WEDNESDAY, Dec. 4, 2002 (HealthDayNews) -- Next time you set a mousetrap, consider this: People and mice share more than 80 percent of the same genes.

That's according to researchers who have mapped the genome of the house mouse, Mus Musculus. The sequencing effort, to be published in tomorrow's issue of Nature, marks only the second complete genetic map of a mammal, and the first since the human genome was released two years ago.

"This is very, very exciting," says Bruce Roe, a molecular biologist at the University of Oklahoma and a member of the sequencing team. Mouse studies are often the first step in testing new drugs and other therapies. So knowing the animal's full genetic map will help scientists develop novel therapies for human disease, Roe explains.

"This gives us a really important basis for comparison," says W. Richard McCombie, a gene sequencing expert at Cold Spring Harbor Laboratory in New York. "It also gives us knowledge about a very useful experimental animal that we can test in."

Scientists are now preparing the genetic blueprint of chimpanzees and dogs, but McCombie says those species may not prove as valuable to human medicine as the mouse.

Mice have between 27,000 and 30,500 genes that generate proteins, roughly the same number as humans. However, the length of their genome, at 2.5 billion nucleotide base pairs, is 14 percent smaller than our 2.9 billion base pair library. Mice and humans diverged from a common ancestor about 75 million years ago.

Protein coding regions constitute only a small fraction of the whole mouse genome, perhaps 1.5 percent to 3 percent. Another 2 percent or so, also highly conserved between humans and mice, consists of genetic material believed to help regulate the expression of genes, the structure of the chromosomes they reside on, and other custodial chores.

That leaves vast tracts of DNA whose functions are a mystery. Because of these large "junk" regions, the genomes of people and mice differ by more than 95 percent, says study co-author Kerstin Lindblad-Toh, a genetics expert at the Whitehead Institute/MIT Center for Genome Research in Cambridge, Mass.

In fact, the junk between protein-coding genes "probably has some sort of vague function," Lindblad-Toh says, such as tempo markings for DNA transcription.

Researchers have had the lay of much of the mouse genome for years, but the full map turned up a few surprises -- including 9,000 new genes in that species and 1,200 previously unknown instructions in humans. The function of most of these is still hazy, Lindblad-Toh says, though one is related to the dystrophin protein that goes awry in muscular dystrophy.

While mice and humans have largely identical protein-coding genomes, some areas are quite different. The rodents have veered off in regions linked to reproduction, immune function and smell, for example. Mice also accumulate errors in uncoded DNA far faster than do humans, Roe says. As a result, the rodents evolve about twice as fast as humans, Lindblad-Toh says, most likely because they are more prone to the whims of their environment than are people.

Dr. Mark S. Boguski, a computational biologist at Seattle's Fred Hutchinson Cancer Research Center, is one of the scientists who will now try to figure out what the mouse genome has to say. Right now, he says, researchers know the rough or specific function of about a third of the human genome, and about the same share of the mouse's.

"Our ability to generate data has far outpaced our ability to analyze it," says Boguski, author of a commentary accompanying the sequencing paper.

Because the information is public, Roe adds, "the data is freely available to the community. My kids can look it up." Funding for the sequencing project came from the National Institutes of Health, as well as other private and public international sources.

What To Do

For more on the mouse genome, try the National Center for Biotechnology Information. Learn about the genetic blueprint for people at the Human Genome Project.

SOURCES: Bruce Roe, M.D., research professor, University of Oklahoma, Norman; Kerstin Lindblad-Toh, Ph.D., senior program manager, Whitehead Institute/MIT Center for Genome Research, Cambridge, Mass.; W. Richard McCombie, Ph.D., Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.; Mark S. Boguski, M.D., Ph.D., investigator, Fred Hutchinson Cancer Research Center, Seattle; Dec. 5, 2002, Nature
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