Researchers devise a new method for determining the purpose of "junk DNA."

Finding a function for the 98.5 percent of our DNA that doesn’t encode for proteins—sometimes known as “junk DNA” for its jumbled, illegible arrangement—became a little less elusive last week. Geneticists from Johns Hopkins published an innovative way of using zebrafish embryos to test the purpose of non-coding human DNA sequences in the March 23rd online issue of Science Express.

“Until recently the strategies required to evaluate [non-coding] sequences frequently required transgenic approaches in mice, which—although informative and valuable—are also expensive and time-consuming,” said the study’s coauthor Andrew McCallion via e-mail. “We used and further developed a novel strategy that uses DNA that can be induced to ‘jump’ into the genome at a high rate significantly improving efficiency.”

The study of non-coding DNA is imperative because within that 98.5 percent of “junk” genetic material reside sequences that control the timing, location and level of proteins encoded within genes, while not actually coding proteins themselves. Consequently they play a significant role in development and disease.

McCallion suggested that junk DNA should actually be thought of as “antique.”

“On first glance, all the furniture looks alike,” he said. “You have to look really hard to decipher what is junk and what is priceless. The proportion that is valuable remains unclear until you have examined a lot of pieces.”

To test these junk strands, researchers link human DNA to marker DNA derived from embryos of other organisms, which carry fluorescent proteins to signal the location and timing of regulatory control displayed by the human DNA.

In the past, scientists had assumed that embryos from organisms that are genetically similar to humans, such as mice, would be more effective, despite the cost and difficulty of producing those embryos. Zebrafish embryos, which are used frequently in large-scale genetic research because of their small size and rapid reproduction cycle, were not considered.

“The existing strategies in zebrafish were not encouraging because of significant problems with efficiency, not to mention that few people would have considered systematically introducing human sequences to test in fish,” McCallion said.

But through experimentation, the Hopkins team discovered that—even though zebrafish DNA sequences looked very different from human sequences—human DNA could still exert regulatory control over zebrafish genes.

This discovery will not only speed up research into junk DNA and lead to better treatment and prevention of congenital diseases, it will also aid in the selection of stem cell lines, as researchers now have an enhanced ability to predict future disorders and mutations through reading the non-coding genetic material.

Originally published March 26, 2006

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