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Of Mouse and Man (video)
December 04, 2002

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Interviewee: Eric Lander, Director of Whitehead MIT Center for Genome Research; Francis Collins, Director of National Human Genome Research Institute.

Video is 1 min 22 sec long. Please be patient while it loads enough to start playing.

Produced by Joyce Gramza

Copyright © ScienCentral, Inc., with additional footage from the Boston Museum of Science, National Institutes of Health (NIH), The Salk Institute, Southern Illinois University School of Medicine, Idea Television, and Nature Publishing Group.

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DNA researchers who sequenced the human genome are now publishing the genome of the laboratory mouse. Why is this so exciting?

As this ScienCentral News video reports, just about all medical advances that benefit human patients are first studied in mice.


Tale of Two Species

Asked to name some examples of human diseases that are studied in mice, Eric Lander, Director of the Whitehead MIT Center for Genome Research, is uncharacteristically dumbstruck. "It's hard to even choose one," he says.

"The mouse is used for studying hundreds and hundreds of different human diseases," says Lander. "It's the best system for biomedical experimentation. We can, in a way that's possible with no other organism, add genes, subtract genes from the mouse, breed it with different mutants, and thereby study human diseases in an experimental setting."

Lander chooses a genetic trait called piebaldism as a vivid example of a physical trait, or phenotype, that correlates with a genetic mutation in both mouse and human.

"There's a great picture I know of a mouse that has a mutation in the gene called cKIT, that prevents the pigment cells from migrating around the body during development. And that mouse has a big white triangular patch on its belly and a white triangular patch on its forehead," he says. "And there's a picture of a human baby who has exactly the same feature... due to a mutation in exactly the same gene. And so we can just look at them and say, the way to study the human condition here is to study the mouse that has exactly the same condition, the same disease."

That's why researchers chose the most common laboratory mouse as the second mammalian genome to sequence after the human genome. The Mouse Sequencing Consortium completed the online draft of the mouse genome in May 2002. Scientists are excited about the official publication of the sequence in the journal Nature because it is accompanied by the first analyses comparing the genomes of mouse and man.

Lining up the two genomes and comparing them, says Lander, is already shedding new light on the human genome. "If you take the text of the human genome and the text of the mouse genome, for every little stretch of one over the course of many millions of letters, you can see the exact spot in the other genome that it lines up with," Lander says.

That's helped researchers revise their estimate of the number of genes in humans, which was already revealed to be surprisingly low--between 30-and 40-thousand genes. "Now with the mouse and the human to compare to each other, it's very clear that the gene counts are almost exactly the same in the two species, and moreover we're able to see that in fact, that count is probably toward the low end of our estimate. By looking at the two, we're able to recognize that some of the stuff we've been counting really isn't genes at all, and I bet the count is going to come out pretty close to about 30-thousand or so for both mouse and human."

"And," Lander adds, "as far as I can tell, [there’s] no significant difference between mouse and human... it's basically the same set of genes, just tinkered with in little ways."

He says the biggest surprise has come from finding similarities in the two genomes that aren't explained by genes. "It turns out that some of the sequence is recognizably being preserved, conserved at a much higher rate than could happen by chance," Lander explains. "That's got to be the stuff that evolution really cares about, the functional stuff.”

Scientists now can reckon that stuff amounts to about 5 percent of the human genome. "And what's really surprising about that 5 percent,” Lander says, “is it's much more than can be explained by the genes. The genes of the human genome can account for maybe two, two and a half percent of that five percent, and what that means is there's another two and a half percent of the genome being lovingly preserved by evolution that matters a lot, and we don't know what it is! So it's a big surprise and it is a complete challenge to the next generation of scientists."

"Far more interesting than answering questions," Lander says, "is discovering that there's a whole new set of questions you didn't even know were there. And that's what's come out of the sequence."

Lander says Whitehead scientists are hard at work now on sequencing another terribly important model animal, the chimpanzee. He predicts that next generation of scientists will devise completely new sorts of experiments with the new set of tools. "Five, ten years from now, any organism you're interested in, you can just have its sequence like that, and we will have its sequence like that. I expect that young kids today by the time they're in college or grad school will just take for granted that they can look up any mammal."

by Joyce Gramza



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