Featured Research

from universities, journals, and other organizations

Comprehensive study using bioinformatics predicts the molecular causes of many genetic diseases

Date:
February 10, 2010
Source:
Buck Institute for Age Research
Summary:
It is widely known that genetic mutations cause disease. What are largely unknown are the mechanisms by which these mutations wreak havoc at the molecular level, giving rise to clinically observable symptoms in patients. Now a new study using bioinformatics reports the ability to predict the molecular cause of many inherited genetic diseases. These predictions have led to the creation of a web-based tool available to academic researchers who study disease.

It is widely known that genetic mutations cause disease. What are largely unknown are the mechanisms by which these mutations wreak havoc at the molecular level, giving rise to clinically observable symptoms in patients. Now a new study using bioinformatics, led by scientists at the Buck Institute for Age Research, reports the ability to predict the molecular cause of many inherited genetic diseases. These predictions involve tens of thousands of genetic disease-causing mutations and have led to the creation of a web-based tool available to academic researchers who study disease.

The research is due to be published online in the February 9, 2010 edition of Human Mutation.

"We now have a quantitative model of function using bioinformatic methods that can predict things like the stability of the protein and how its stability is disrupted when a mutation occurs," said Buck Institute faculty member Sean Mooney, PhD, who led the research team. "Traditionally people have used a very time consuming process based on evolutionary information about protein structure to predict molecular activity," Mooney said, "I think we're the first group to really quantitatively describe the universe of molecular functions that cause human genetic disease."

The research was done in the contexts of inherited single gene diseases, complex diseases such as cardiovascular and developmental disorders and mutations in cancerous tumors. The study focused on amino acid substitutions (AAS), which are genetically driven changes in proteins that can give rise to disease, and utilized a series of complex mathematical algorithms to predict activity stemming from the mutations.

As a first step, researchers used available databases of known sites of protein function and built mathematical algorithms to predict new sites of protein function said Mooney. They then applied the algorithms to proteins that have disease-associated mutations assigned to them and looked for statistical co-occurrences of mutations that fell in or near those functional sites. Because the computer algorithms are imperfect, researchers compared that information against a data set of neutral AAS, ones that don't cause human disease, said Mooney. "We looked for statistical differences between the percentage of mutations that fell into the same functional site from both non-disease and disease-associated AAS and looked to see if there was a statistically significant enrichment or depletion of protein activity based on the type of AAS . That data was used to hypothesize the molecular mechanism of genetic disease," said Mooney.

Mooney says 40,000 AAS were analyzed which represents one of the most comprehensive studies of mutations. Describing the results, he used the analogy of a car as a protein -- a big molecular machine. "We are predicting how this machine will break down," said Mooney. "We've known the car isn't working properly because it has some defect; now we can hypothesize that the symptom stems from a broken water pump."

The web tool, designed to enhance the functional profiling of novel AAS, has been made available at http://www..mutdb.org/profile. Mooney identified three different areas of research that could be furthered by use of the tool. Scientists who manage databases of clinically observed mutations for research purposes could develop hypotheses about what those mutations are causing on a molecular level; they may also be able to use the tool to correlate molecular activity to the clinical severity or subtype of a disease. Mooney says cancer researchers re-sequencing tumors could use the tool to identify mutations that drive the progression of the malignancy. He also expects non-clinical researchers who work with mutations in proteins to use the tool to gain insight into what is causing the mutations. "We are happy to collaborate with scientists, to share data and help them better identify hypotheses about the specific mutations they might be interested in," said Mooney.


Story Source:

The above story is based on materials provided by Buck Institute for Age Research. Note: Materials may be edited for content and length.


Cite This Page:

Buck Institute for Age Research. "Comprehensive study using bioinformatics predicts the molecular causes of many genetic diseases." ScienceDaily. ScienceDaily, 10 February 2010. <www.sciencedaily.com/releases/2010/02/100209152221.htm>.
Buck Institute for Age Research. (2010, February 10). Comprehensive study using bioinformatics predicts the molecular causes of many genetic diseases. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2010/02/100209152221.htm
Buck Institute for Age Research. "Comprehensive study using bioinformatics predicts the molecular causes of many genetic diseases." ScienceDaily. www.sciencedaily.com/releases/2010/02/100209152221.htm (accessed April 19, 2014).

Share This



More Plants & Animals News

Saturday, April 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Vermont Goat Meat Gives Refugees Taste of Home

Vermont Goat Meat Gives Refugees Taste of Home

AP (Apr. 18, 2014) Dairy farmers and ethnic groups in Vermont are both benefiting from a unique collaborative effort that's feeding a growing need for fresh and affordable goat meat. (April 18) Video provided by AP
Powered by NewsLook.com
Man Claims He Found Loch Ness Monster With... Apple Maps?

Man Claims He Found Loch Ness Monster With... Apple Maps?

Newsy (Apr. 18, 2014) Andy Dixon showed the Daily Mail a screenshot of what he believes to be the mythical beast swimming just below the lake's surface. Video provided by Newsy
Powered by NewsLook.com
First Ever 'Female Penis' Discovered In Animal Kingdom

First Ever 'Female Penis' Discovered In Animal Kingdom

Newsy (Apr. 18, 2014) Not only are these newly discovered bugs' sex organs reversed, but they also mate for up to 70 hours. 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

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