Featured Research

from universities, journals, and other organizations

New Method Simplifies Search For Genetic Changes Associated With Disease

Date:
January 18, 2005
Source:
Washington University School Of Medicine
Summary:
It is now significantly easier to search long stretches of DNA for genetic changes associated with disease, thanks to scientists at Washington University School of Medicine in St. Louis.

St. Louis, January 4, 2005 -- It is now significantly easier to search long stretches of DNA for genetic changes associated with disease, thanks to scientists at Washington University School of Medicine in St. Louis.

The researchers developed a method called direct genomic selection that accelerates the transition between family or population-based studies of disease inheritance patterns and identification of genetic variations that may contribute to disease. That transition normally slows down dramatically when scientists have to sequence regions of interest in patients' DNA, determining the letter-by-letter genetic code found in those regions.

With the base sequences from many patients' DNA, scientists can conduct comparisons that highlight the changes most commonly linked to disease, providing them the leads they need to better understand and treat a wide range of disorders.

Researchers report in the January issue of Nature Methods that they've already applied direct genomic selection to a region of DNA linked to psoriasis, a disfiguring and potentially debilitating inherited skin condition.

"We quickly found 100 previously unidentified genetic variations with potential links to psoriasis," says senior author Michael Lovett, Ph.D., professor of genetics and pediatrics. "It really is a much quicker and more affordable way of getting at these types of variations and has potential for applications in other areas including cancer research."

Lovett is working with colleagues at the Genome Sequencing Center (GSC) at Washington University School of Medicine to make direct genomic selection available to a much wider group of researchers. The approach will further empower the University's BioMed 21 initiative, which is dedicated to harnessing genetic studies and other basic research for improved patient diagnosis and treatment.

"This is a major technological breakthrough," says Mark Johnston, Ph.D., professor and chair of the Department of Genetics. "It's clearly an enabling technology that will let us extract the region of interest from each individual's DNA and sequence it."

Direct genomic selection answers a growing need for what geneticists call resequencing -- sequencing the same genetic region in many individuals.

Scientists measure DNA by its individual units of code, which are known as base pairs. Current automated DNA sequencing technology can process pieces of DNA 700 to 1,000 base pairs long, but inheritance studies can leave researchers searching for changes in segments of DNA hundreds of times longer.

Scientists formerly had only two unattractive options for circumventing this disparity and sequencing such large regions. One, which reproduces patients' entire genomes, can take up to a year, costs tens of thousands of dollars and discards most of the genetic material produced. The other uses a process that focuses more directly on the region of interest in patients' DNA but leaves the genetic materials in a state that requires considerable time and effort to prepare them for sequencing.

Direct genomic selection both zeroes in on the region of interest and produces genetic material in a form that can easily be prepared for automated sequencing systems, according to Lovett.

Direct genomic selection crafts what Lovett calls "fishing rods" from genetic material produced and maintained by the Human Genome Project. For that project, researchers divided the human genome into many sections and copied the sections into bacterial artificial chromosomes (BACs), structures they implanted in bacteria for easy reproduction of DNA.

Scientists interested in a particular region of the human genome can now order the BAC of that region from the genome project and use Lovett's procedure to modify the BAC with biochemical hooks, making it possible to fish out the corresponding region from a patient's DNA for sequencing.

Lovett also developed modifications to the steps used to prepare patient DNA. The steps ensure that the material snared by the fishing rods can easily be prepared for sequencing.

"The challenge now is that we have many disease genes that are not all-or-nothing factors--they can be linked to increased risk of disease, but not to guaranteed development of the disease," Lovett explains. "In some such instances, there's concern that another gene or bit of genetic code sitting somewhere nearby, in the same approximate region, might be able to more completely explain what happens in the disease."

Direct genomic selection should also be helpful to cancer research, according to Lovett.

"In many cancer cases we know there are alterations in the DNA of cancer cells--deletions, additions, or substitutions," Lovett says. "We've had great difficulty in narrowing those differences down, but direct genomic selection could help scientists go in, grab the appropriate region of DNA, sequence it and start to learn what's going on."

###

Bashiardes S, Veile R, Helms C, Mardis ER, Bowcock AM, Lovett M. Direct genomic selection: Overcoming a technical hurdle in identifying variation and mutations in large genomic regions. Nature Methods, January 2005.

Funding from the National Institutes of Health supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "New Method Simplifies Search For Genetic Changes Associated With Disease." ScienceDaily. ScienceDaily, 18 January 2005. <www.sciencedaily.com/releases/2005/01/050110121010.htm>.
Washington University School Of Medicine. (2005, January 18). New Method Simplifies Search For Genetic Changes Associated With Disease. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2005/01/050110121010.htm
Washington University School Of Medicine. "New Method Simplifies Search For Genetic Changes Associated With Disease." ScienceDaily. www.sciencedaily.com/releases/2005/01/050110121010.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins