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Powerful genome ID method extended to humans
October 10, 2006For cancer biology and other medical applications, optical mapping reveals more than traditional DNA sequencing
A mathematical discovery has extended the reach of a novel genome mapping method to humans, potentially giving cancer biology a faster and more cost-effective tool than traditional DNA sequencing.
A student-led group from the laboratory of Michael Waterman, USC University Professor in molecular and computational biology, has developed an algorithm to handle the massive amounts of data created by a restriction mapping technology known as "optical mapping." Restriction maps provide coordinates on chromosomes analogous to mile markers on freeways.
Lead author Anton Valouev, a recent graduate of Waterman's lab and now a postdoctoral fellow at Stanford University, said the algorithm makes it possible to optically map the human genome.
"It carries tremendous benefits for medical applications, specifically for finding genomic abnormalities," he said.
The algorithm appears in this week's PNAS Early Edition.
Optical mapping was developed at New York University in the late 1990s by David Schwartz, now a professor of chemistry and genetics at the University of Wisconsin-Madison. Schwartz and a collaborator at Wisconsin, Shiguo Zhou, co-authored the PNAS paper.
The power of optical mapping lies in its ability to reveal the size and large-scale structure of a genome. The method uses fluorescence microscopy to image individual DNA molecules that have been divided into orderly fragments by so-called restriction enzymes.
By imaging large numbers of an organism's DNA molecules, optical mapping can produce a map of its genome at a relatively low cost.
An optical map lacks the minute detail of a genetic sequence, but it makes up for that shortcoming in other ways, said Philip Green, a professor of genome sciences at the University of Washington who edited the PNAS paper.
Geneticists often say that humans have 99.9 percent of their DNA in common. But, Green said, "individuals occasionally have big differences in their chromosome structure. You sometimes find regions where there are larger changes."
Such changes could include wholesale deletions of chunks of the genome or additions of extra copies. Cancer genomes, in particular, mutate rapidly and contain frequent abnormalities.
"That's something that's very hard to detect" by conventional sequencing, Green said, adding that sequencing can simply miss part of a genome.
Optical mapping, by contrast, can estimate the absolute length of a genome and quickly detect differences in length and structure between two genomes. Comparing optical maps of healthy and diseased genomes can guide researchers to crucial mutations.
Though he called optical mapping "potentially very powerful," Green added that it requires such a high level of expertise that only a couple of laboratories in the world use the method.
The Waterman group's algorithm may encourage others to take a second look.
University of Southern California
Lead author Anton Valouev, a recent graduate of Waterman's lab and now a postdoctoral fellow at Stanford University, said the algorithm makes it possible to optically map the human genome.
"It carries tremendous benefits for medical applications, specifically for finding genomic abnormalities," he said.
The algorithm appears in this week's PNAS Early Edition.
Optical mapping was developed at New York University in the late 1990s by David Schwartz, now a professor of chemistry and genetics at the University of Wisconsin-Madison. Schwartz and a collaborator at Wisconsin, Shiguo Zhou, co-authored the PNAS paper.
The power of optical mapping lies in its ability to reveal the size and large-scale structure of a genome. The method uses fluorescence microscopy to image individual DNA molecules that have been divided into orderly fragments by so-called restriction enzymes.
By imaging large numbers of an organism's DNA molecules, optical mapping can produce a map of its genome at a relatively low cost.
An optical map lacks the minute detail of a genetic sequence, but it makes up for that shortcoming in other ways, said Philip Green, a professor of genome sciences at the University of Washington who edited the PNAS paper.
Geneticists often say that humans have 99.9 percent of their DNA in common. But, Green said, "individuals occasionally have big differences in their chromosome structure. You sometimes find regions where there are larger changes."
Such changes could include wholesale deletions of chunks of the genome or additions of extra copies. Cancer genomes, in particular, mutate rapidly and contain frequent abnormalities.
"That's something that's very hard to detect" by conventional sequencing, Green said, adding that sequencing can simply miss part of a genome.
Optical mapping, by contrast, can estimate the absolute length of a genome and quickly detect differences in length and structure between two genomes. Comparing optical maps of healthy and diseased genomes can guide researchers to crucial mutations.
Though he called optical mapping "potentially very powerful," Green added that it requires such a high level of expertise that only a couple of laboratories in the world use the method.
The Waterman group's algorithm may encourage others to take a second look.
University of Southern California
Genome Current Events and Genome News RSSTime of day matters to thirsty trees, U of T researcher discovers
The time of day matters to forest trees dealing with drought, according to a new paper produced by a research team led by Professor Malcolm Campbell, University of Toronto Scarborough's vice-principal for research and colleagues in the department of cell and systems biology at the St. George campus.
Genetic analysis helps dissect molecular basis of cardiovascular disease
Using highly precise measurements of plasma lipoprotein concentrations determined by nuclear magnetic resonance spectroscopy (NMR), researchers led by Daniel Chasman at Brigham and Women's Hospital and Harvard Medical School in Boston, MA, the Framingham Heart Study in Framingham, and the PROCARDIS consortium in Stockholm, Sweden and Oxford, England performed genetic association analysis across the whole genome among 17,296 women of European ancestry from the Women's Genome Health Study.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
Scientists at UA, collaborating institutions decode maize genome
Scientists from the University of Arizona led by Arizona Genomics Institute director Rod A. Wing and from collaborating institutions have deciphered the complete genetic code of the maize plant for the first time.
Ancestry attracts, but love is blind
People preferentially marry those with similar ancestry, but their decisions are not necessarily based on hair, eye or skin colour.
WPI Researchers Take Aim at Hard-to-Treat Fungal Infections
A team of researchers at the Worcester Polytechnic Institute (WPI) Life Sciences and Bioengineering Center at Gateway Park has developed a new model system to study fungal infections.
Technique finds gene regulatory sites without knowledge of regulators
A new statistical technique developed by researchers at the University of Illinois allows scientists to scan a genome for specific gene-regulatory regions without requiring prior knowledge of the relevant transcription factors.
Causative gene of a rare disorder discovered by sequencing only protein-coding regions of genome
For the first time, scientists have successfully used a method called exome sequencing to quickly discover a previously unknown gene responsible for a mendelian disorder.
New research into the mechanisms of gene regulation
A team led by Penn State's Ross Hardison, T. Ming Chu Professor of Biochemistry and Molecular Biology, has taken a large step toward unraveling how regulatory proteins control the production of gene products during development and growth.
Maize cell wall genes identified, giving boost to biofuel research
Purdue University scientists have helped identify and group the genes thought to be responsible for cell wall development in maize, an effort that expands their ability to discover ways to produce the biomass best suited for biofuels production.
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