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Powerful genome barcoding system reveals large-scale variation in human DNA
Date:5/31/2010

me are often found within DNA's trickiest stretches.

"Short pieces could really come from so many different locations," Teague says. "An enormous part of the genome is composed of repeating DNA, and important differences are often associated with areas that have a lot of repeated sections."

It's a problem inherent to the method that has irked Schwartz for a long time.

"Our new technology quickly analyzes huge DNA molecules one at a time, which eliminates the copy machine step, reduces the number of DNA jig-saw pieces and increases the unique qualities of each piece," Schwartz says. "These advantages allow us to discover novel genetic patterns that are otherwise invisible."

The genome mapping system in Schwartz' lab takes in much larger pieces, at least millions of base pairs at a time. Sub-millimeter sections of single DNA molecules thread-like and, in full, 4 to 5 inches long in humans are coaxed onto treated glass surfaces.

The long strands of DNA straighten out on the glass, and are clipped into sections by enzymes and scanned by automated microscopes. The pattern of these cuts along each molecule thread produces a unique barcode, identifying the DNA molecule and revealing genetic changes it harbors.

The scan results are passed along to databases for storage and retrieval, and handled by software that stitches collections of bar-coded molecules together with others to reconstitute the entire strand of DNA and quickly pinpoint genetic changes.

"What we have here is a genetic version of Google Earth," Schwartz says. "I could sit down with you and start at chromosome 1, and we could pan and zoom through each one and actually see the genetic changes across an individual's genome."

To Teague, the Optical Mapping System provides access to a new frame of reference on human genetic variation.

"I've got a whole folder of papers on diseases that are ascribable to these structural differences
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Contact: David C. Schwartz
dcschwartz@wisc.edu
608-265-0546
University of Wisconsin-Madison
Source:Eurekalert

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