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 October 25, 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 October 25, 2014).

Share This



More Plants & Animals News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. 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:

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