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Genetic code reading easier as Brown physicists slow DNA

5:47 PM Fri, Apr 24, 2009 |
C. Eugene Emery Jr.    Email

PROVIDENCE -- Brown University researchers have developed a way to slowly draw an individual strand of DNA through a microscopic pore so its genetic code can be read quickly.

The discovery could pave the way for sequencing a person's code in as little as an hour.

The first time human DNA was analyzed, a project begun in 1990, it took 13 years and cost $3 billion. The hope is that if you know your DNA profile, doctors will be able to predict -- and possibly help you avoid -- important health problems.

The work is a step closer to making that practical, according to Brown physicist Xinsheng Sean Ling, one of the authors of the new study.

Even though the genetic code consists of only four letters, known as base pairs, the challenge of reading one's DNA is immense. Humans have 3.3 billion base pairs.

In theory, one way to rapidly read the code is to use an electric field to draw a DNA strand through a tiny pore. At the pore, telltale changes in the electric field around the pore tell researchers which of the four base pairs is passing through at any particular instant.

There's only one problem: when the electric field is applied, DNA moves through the pore too quickly -- at 50 million base pairs per second -- to be read accurately.

Ling and his former graduate student Hongbo Peng, who now works at IBM, found a way to slow it down.

They attached one end of the DNA strand to a microscopic bead that was larger than the pore. Next, they used the electric field to thread the unattached end of the DNA through the pore. The DNA tried to pass all the way through, but the bead prevented that.

Finally, they used a magnetic field to draw the bead back away from the pore. As the pore withdrew, it pulled the DNA strand with it. The result was a tug of war, as the electric field tried to pull the DNA in one direction and the bead, drawn away by the magnetic field, pulled the DNA in the other.

By varying the strength of each field, the scientists were able to control the speed at which the DNA passed through the pore.

Having it slip through at a rate of 10,000 base pairs per second is slow enough to have each individual base pair read accurately.

"Anything faster than that is too fast" Ling said.

With 100 pores reading genetic code simultaneously, he said, all 3.3 billion base pairs could be logged in an hour.

The system is also flexible, allowing the DNA to pass through the pore even more slowly.

"We provide a means by which the reading mechanism becomes possible," Ling said.

The researchers now plan to test the technique using DNA from bacteria.

The experimental system is small -- only about one inch square. But if a company decided to develop the technology, it could be even more compact, he said.

The findings are reported in the journal Nanotechnology, which deals with extremely tiny technology.

A strand of DNA is about 2.5 nanometers wide. The pore used to read it was 10 nanometers wide. The bead used to anchor the DNA was 2,800 nanometers across. In contrast, the width of a typical human hair is 100,000 nanometers.

gemery@projo.com / (401)277-7442

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Comments

sally manuel said:

I for one say thank you. I lost my husband of 29 years to a gentic disease called huntingtons disease in Jan and each advance is a step toward maybe one day a cure to this and many other things.
We waited 3 months years ago to find out his test results, a long three months.
I praise anyone in research for medical science advancement.




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