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From Wired:

Singling Out the Fruit Fly Gene
by Kristen Philipkoski
3:00 a.m. Jun. 19, 2000 PDT

Researchers have discovered a technique they've sought for over 20 years: a way to turn off specific genes in the fruit fly.

University of Utah researchers created the so-called "knock-out" technology –- a technique that gives scientists the ability to create model organisms and compare them with humans to learn more about the cause and possible therapies for disease. Until now, the technology was possible in yeast and mice, but not the fruit fly.

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See also: Error in Genome Done on the Fly

The sequence of the entire genetic make-up of the fruit fly was mapped last September by researchers at the University of California at Berkeley, and Celera Genomics of Rockville, Maryland.

"It will make the (fruit fly) sequence much more valuable now that this technique is in hand," said Yikang Rong, a post-doctoral researcher in the biology department at the University of Utah.

For decades, fly geneticists have cross-bred fruit flies in order to study their genes, but there was never a way to directly manipulate specific genes until now.

The paper on the discovery has generated "tons" of interest from other researchers wanting to try the technique.

When researchers finished mapping the whole Drosophila genome, they found that an unexpectedly large number of genes that are closely related to genes that exist in humans.

"With the new strategy we now have the ability to take the information that we know now from having the complete Drosophila genome, and directly manipulate specific genes," said Paul Wolfe, program director in the division of genetics and developmental biology at the National Institute of General Medical Science, which provided funding for the research.

The NIGMS started the "R21" high-risk, high-impact research funding program two years ago for experiments like Rong's that are too risky to receive traditional grants but have a potentially high payoff.

Drosophila researchers now have the ability to single out any one of the organisms' more than 13,000 genes and turn it off.
So far, researchers have discovered 289 genes in humans that when mutated cause disease. Of these, there are 177 that have direct counterparts in the fruit fly.

"Since there are these close similarities, you can find the genes that have similarities between the two organisms and knock them out in the fly and ask what happens," Wolfe said. "They might have some disease role."

Flies and humans share many features like hair, eyes, and several developmental processes such as learning, behavior, and memory, at least at the early stages. By knocking out the genes responsible for these functions in the fruit fly, researchers will create models to study the corresponding genes in humans and learn more about disease, Wolfe said.

Rong began trying to discover a knock-out technique for the fruit fly as a graduate student in 1994. He changed some components of the technique and began working on it full time as a post doc at Utah in 1998.

The technique that Rong developed with Kent Golic, another biology researcher at Utah, allows researchers to either knock out genes in fruit flies or knock them "in" by introducing a particuar gene into the fly genome -– a basic principle of gene therapy. p>

They did the experiment on a strain of fruit fly that has a yellow instead of brown body color. By specially manipulating the gene that controls the fly's body color, the next generation of the flies were brown.

It's a fairly simple technique that the Utah researchers said they hope will be used on organisms other than the fruit fly.

"The fact that we could use the same technology in other organisms is really exciting because the way we did it does not require any fly-specific tricks," Rong said. "In theory, it could be done in any organisms (into which) you can introduce a foreign piece of DNA," Rong said.

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