Featured Research

from universities, journals, and other organizations

Will a genetic mutation cause trouble? Ask Spliceman

Date:
March 5, 2012
Source:
Brown University
Summary:
New, free Web-based software analyzes DNA sequences to determine if mutations are likely to cause errors in splicing of messenger RNA. When gene splicing goes awry, a wide variety of diseases can result.

Last year a team of Brown researchers, from left: Luciana Ferraris, Kian Huat Lim, William Fairbrother, Madeleine Filloux, published a paper in the Proceedings of the Nationa Academy of Sciences that used Spliceman to link more disease-causing mutations than previously thought to problems with splicing.
Credit: Mike Cohea/Brown University

New, free Web-based software described in the journal Bioinformatics analyzes DNA sequences to determine if mutations are likely to cause errors in splicing of messenger RNA. When gene splicing goes awry, a wide variety of diseases can result.

Related Articles


In a brief paper in the journal Bioinformatics, Brown University researchers describe a new, freely available Web-based program called Spliceman for predicting whether genetic mutations are likely to disrupt the splicing of messenger RNA, potentially leading to disease.

"Spliceman takes a set of DNA sequences with point mutations and computes how likely these single nucleotide variants alter splicing phenotypes," write co-authors Kian Huat Lim, a graduate student, and William Fairbrother, assistant professor of biology, in an "application note" published in advance online Feb. 10. It will appear in print in April.

Spliceman can be found at fairbrother.biomed.brown.edu/spliceman.

The software is based on research published last year in the Proceedings of the National Academy of Sciences, in which Fairbrother's group used Spliceman to show that perhaps as many as a third of the disease-causing mutations in the Human Genome Mutation Database do so by causing errant gene splicing.

Splicing of RNA, based on instructions in DNA, is like a film editing process. A gene includes raw footage and instructions on how it should be edited to produce a protein. If the editing instructions are faulty, the scenes extracted from the raw footage may be spliced together in the wrong order or the wrong scenes might be used.

Each of a person's 20,000 genes has about 20 splice sites. Sequences that regulate splicing often occur close to splice sites, and every possible "word" of DNA letters (e.g. AAA) has a signature distribution around the splice sites. But a mutation creates a new word. For example, an A-to-T mutation could change "AAA" to "ATA." In a normal genome, if AAA encodes proper splicing, its average distance to the nearest splice site will be short and if ATA doesn't encode proper splicing its distance would be longer. A mutation that changes a word close to splicing sites into one that is typically found far from splicing sites would be of particular concern because it could have a likely adverse effect on splicing.

"The bigger the distance, the more likely that it affects splicing," Lim said.

Spliceman makes its predictions about mutations by calculating that distance. It has successfully predicted the known effect of many mutations.

The software has genomic information about 11 species: humans, chimpanzees, rhesus monkeys, mice, rats, dogs, cats, chickens, guinea pigs, frogs, and zebra fish.

Fairbrother said he has already heard from colleagues and medical researchers who have been eager to integrate Spliceman into their efforts.

"I think it will mostly be used by medical geneticists seeking to understand the cause of disease," he said.

One use of the software, Fairbrother said, will be by a Harvard-based multidisciplinary team led by genetics researcher Shamil Sunyaev in this year's Children's Hospital Boston CLARITY challenge.

In the contest, competitors must discover the unknown genetic basis of rare disorders faced by three pediatric patients. Armed with the entire genome sequence of the patients and their parents, Spliceman will be used to interrogate discovered mutations and variants for their ability to disrupt splicing.

The National Institutes of Health has funded Fairbrother's research.


Story Source:

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


Journal References:

  1. K. H. Lim, L. Ferraris, M. E. Filloux, B. J. Raphael, W. G. Fairbrother. Using positional distribution to identify splicing elements and predict pre-mRNA processing defects in human genes. Proceedings of the National Academy of Sciences, 2011; 108 (27): 11093 DOI: 10.1073/pnas.1101135108
  2. K. H. Lim, W. Fairbrother. Spliceman - A computational web server that predicts sequence variations in pre-mRNA splicing. Bioinformatics, 2012; DOI: 10.1093/bioinformatics/bts074

Cite This Page:

Brown University. "Will a genetic mutation cause trouble? Ask Spliceman." ScienceDaily. ScienceDaily, 5 March 2012. <www.sciencedaily.com/releases/2012/03/120305132440.htm>.
Brown University. (2012, March 5). Will a genetic mutation cause trouble? Ask Spliceman. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2012/03/120305132440.htm
Brown University. "Will a genetic mutation cause trouble? Ask Spliceman." ScienceDaily. www.sciencedaily.com/releases/2012/03/120305132440.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Anglerfish Rarely Seen In Its Habitat Will Haunt You

Anglerfish Rarely Seen In Its Habitat Will Haunt You

Newsy (Nov. 22, 2014) For the first time Monterey Bay Aquarium recorded a video of the elusive, creepy and rarely seen anglerfish. Video provided by Newsy
Powered by NewsLook.com
Birds Around the World Take Flight

Birds Around the World Take Flight

Reuters - Light News Video Online (Nov. 22, 2014) An imperial eagle equipped with a camera spreads its wings over London. It's just one of the many birds making headlines in this week's "animal roundup". Jillian Kitchener reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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