Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Powerful genome barcoding system reveals large-scale variation in human DNA

01.06.2010
Genetic abnormalities are most often discussed in terms of differences so miniscule they are actually called "snips" — changes in a single unit along the 3 billion that make up the entire string of human DNA.

"There's a whole world beyond SNPs — single nucleotide polymorphisms — and we've stepped into that world," says Brian Teague, a doctoral student in genetics at the University of Wisconsin-Madison. "There are much bigger changes in there."

Variation on the order of thousands to hundreds of thousands of DNA's smallest pieces — large swaths varying in length or location or even showing up in reverse order — appeared 4,205 times in a comparison of DNA from just four people, according to a study published May 31 in the Proceedings of the National Academy of Sciences.

Those structural differences popped into clear view through computer analysis of more than 500 linear feet of DNA molecules analyzed by the powerful genome mapping system developed over nearly two decades by David C. Schwartz, professor of chemistry and genetics at UW-Madison.

"We probably have the most comprehensive view of the human genome ever," Schwartz says. "And the variation we're seeing in the human genome is something we've known was there and important for many years, but we haven't been able to fully study it."

To get a better picture of those structural variations, Schwartz and his team developed the Optical Mapping System, a wholly new type of genome analysis that directly examines millions of individual DNA molecules.

Common systems for analyzing genomes typically chop long DNA molecules into fragments less than a couple thousand base pairs long and multiply them en masse, like a copy machine, to develop a chemical profile of each piece.

Reading such small sections without seeing their place in the larger picture of DNA leaves out critical understanding. To make matters worse, interesting parts of the human genome 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," he says. "If you can see the genetic basis for those diseases, you can figure out the molecular differences in their development and pick drug targets to treat or cure or avoid them altogether. We fit into that storyline right up at the front."

It's been a long story.

"We've been thinking about these large structural variations for decades," says Schwartz, whose work is funded by the National Institutes for Health and the National Science Foundation. "The problem was that the system for discerning large structural variants was not available. So we had to build it."

The integrative building process included studying the behavior of fluids at microscopic scale, manipulating large DNA molecules and placing barcodes on them, automating high-powered microscopes to analyze single molecules, organizing the computing infrastructure to handle the data and algorithms to analyze whole human genome, and more.

And after notable turns analyzing the DNA of corn, parasites, bacteria and even the mold that caused the 19th-century potato famine in Ireland, Schwartz has arrived at the human genome, his original target.

"It's like you spend years making a telescope, and then one day you point it at the sky and you discover things that no one else could see," he says. "We've integrated so many scientific problems together in a holistic way, which lets us solve very hard problems."

The result is a 30-day turnaround for one graduate student to analyze one human genome, but that's just a waypoint. Schwartz's team isn't just pointing at the sky. They are aiming for the stars by building new systems for personal genomics.

"This will go even further," says Konstantinos Potamousis, the lab's instrumentation innovator and a co-author on the study, which included researchers from UW-Madison, Mississippi State University, the University of Pittsburgh, the University of Southern California and the University of Washington. "Our systems scale nicely into the future because we've pioneered single molecule technologies. The newer systems we are building will provide more genetic information in far less time."

With development complete on new molecular devices, software and analysis, a large piece of the system is already in place.

And the speed of innovation will synergize the pace of genome analysis.

"Our newer genome analysis systems, if commercialized, promise genome analysis in one hour, at under $1,000," Schwartz says. "And we require that high speed and low cost to power the new field of personal genomics."

David C. Schwartz | EurekAlert!
Further information:
http://www.wisc.edu

More articles from Life Sciences:

nachricht Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory

nachricht ‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

Im Focus: A transistor of graphene nanoribbons

Transistors based on carbon nanostructures: what sounds like a futuristic dream could be reality in just a few years' time. An international research team working with Empa has now succeeded in producing nanotransistors from graphene ribbons that are only a few atoms wide, as reported in the current issue of the trade journal "Nature Communications."

Graphene ribbons that are only a few atoms wide, so-called graphene nanoribbons, have special electrical properties that make them promising candidates for the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

Blockchain is becoming more important in the energy market

05.12.2017 | Event News

 
Latest News

Making fuel out of thick air

08.12.2017 | Life Sciences

Rules for superconductivity mirrored in 'excitonic insulator'

08.12.2017 | Information Technology

Smartphone case offers blood glucose monitoring on the go

08.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>