Featured Research

from universities, journals, and other organizations

Statistical Analysis Could Yield New Drug Target For Multiple Sclerosis

Date:
February 17, 2009
Source:
Rockefeller University
Summary:
An elaborate statistical analysis of genes from more than 7,000 individuals has identified an amino acid that appears to be a major risk factor for multiple sclerosis, a devastating autoimmune disorder that afflicts 2.5 million people worldwide.

An elaborate statistical analysis of genes from more than 7,000 individuals has identified an amino acid that appears to be a major risk factor for multiple sclerosis, a devastating autoimmune disorder that afflicts 2.5 million people worldwide.

In research published this month in BMC Medical Genetics, scientists from The Rockefeller University and colleagues from the University of Oxford in England and the University of British Columbia in Canada report a binding pocket in a previously implicated gene that may be an attractive research prospect as a potential drug target.

The analysis by biostatistician Knut M. Wittkowski, of Rockefeller’s Center for Clinical and Translational Science, is the most sweeping to date of a database containing disease-relevant genes of 13,000 individuals who either have multiple sclerosis or are closely related to someone who does. Wittkowski and colleagues focused on a gene identified about a year ago in the New England Journal of Medicine as the single most important genetic risk factor for multiple sclerosis. The gene, HLA-DRB1, is part of the major histocompatibility complex, a large cluster of particularly complex genes evolved to help the immune system adaptively respond to foreign invaders that it has never before encountered. How it contributes to the disease remains a mystery, however.

Unlike most human genes, which have only two alleles per locus, HLA-DRB1 has up to four, making traditional statistical analyses problematic. Wittkowski extended a variant of a commonly used method he developed in 2002 with a postdoc from Rockefeller’s Laboratory of Statistical Genetics to deal with multi-allelic loci so that it could handle the complexity of HLA-DRB1. He analyzed 93 locations with genetic variations and found that a single amino acid in the protein that the gene encodes, number 13, is the telltale indicator of susceptibility to multiple sclerosis. Amino acid 13 is at the center of a pocket in the HLA-DRB1 molecule that helps present an invading pathogen to the immune cells that can kill it. The researchers speculate that a mutation in this amino acid could cause the molecule to present healthy tissue for execution, one of the possible ways multiple sclerosis attacks the body.

“We have identified the most important part of the gene for MS risk,” says Sreeram Ramagopalan, a postdoctoral research fellow at Oxford’s Wellcome Trust Center for Human Genetics, who collaborated with Wittkowski. “And it looks plausible. Amino acid 13 is part of a piece of the molecule that presents peptides to trigger the immune reaction.”

Although multiple sclerosis is a complicated disease that likely has other genetic as well as environmental risk factors, the collaboration between Wittkowski and clinical and translational colleagues has provided researchers a specific hypothesis to explore. “It is rare to find investigators who are open to developing new statistical methods to address the data at hand,” Wittkowski says. “This is the type of transformative result a real collaboration can produce beyond the more common consultation about off-the-shelf methods.”

Ramagopalan says his researchers at Oxford will be following up on the statistical analysis with wet-lab experiments using animal models to detail the role amino acid 13 plays. “Now we want to know exactly how it works and what happens without it or when it is changed,” he says.


Story Source:

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


Journal Reference:

  1. Ramagopalan et al. An extension to a statistical approach for family based association studies provides insights into genetic risk factors for multiple sclerosis in the HLA-DRB1 gene. BMC Medical Genetics, 2009; 10 (1): 10 DOI: 10.1186/1471-2350-10-10

Cite This Page:

Rockefeller University. "Statistical Analysis Could Yield New Drug Target For Multiple Sclerosis." ScienceDaily. ScienceDaily, 17 February 2009. <www.sciencedaily.com/releases/2009/02/090213103053.htm>.
Rockefeller University. (2009, February 17). Statistical Analysis Could Yield New Drug Target For Multiple Sclerosis. ScienceDaily. Retrieved August 29, 2014 from www.sciencedaily.com/releases/2009/02/090213103053.htm
Rockefeller University. "Statistical Analysis Could Yield New Drug Target For Multiple Sclerosis." ScienceDaily. www.sciencedaily.com/releases/2009/02/090213103053.htm (accessed August 29, 2014).

Share This




More Health & Medicine News

Friday, August 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com
Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. 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