Featured Research

from universities, journals, and other organizations

Uncovering the cause of a common form of muscular dystrophy: Research team makes second critical advance

Date:
October 28, 2010
Source:
Fred Hutchinson Cancer Research Center
Summary:
An international team of researchers has made a second critical advance in determining the cause of a common form of muscular dystrophy known as facioscapulohumeral dystrophy, or FSHD.

An international team of researchers led by an investigator from Fred Hutchinson Cancer Research Center has made a second critical advance in determining the cause of a common form of muscular dystrophy known as facioscapulohumeral dystrophy, or FSHD.

Related Articles


In August 2010 the group published a landmark study that established a new and unifying model for the cause of FSHD. The current work, published Oct. 28 in PLoS Genetics, shows that the disease is caused by the inefficient suppression of a gene that is normally expressed only in early development. The work will lead to new approaches for therapy and new insights into human evolution.

The disease-causing gene, called DUX4, previously had been thought to be a completely inactive gene in humans. DUX4 belongs to a special class of genes called retrogenes, which usually represent unused byproducts of evolution that have no remaining biological function, sometimes called "dead genes."

In contrast, the researchers discovered that the DUX4 protein is abundantly expressed in human germ-line cells, the cells that form the sperm and eggs, which indicates a necessary function early in development. Normally, the DUX4 gene is suppressed in all other cells of the body. However, the mutation that causes FSHD makes this suppression less efficient.

"The result is that the DUX4 gene occasionally escapes the inefficient suppression and is expressed in some muscle cells, similar to the Old Faithfull geyser that is usually off but occasionally releases a burst of water," said corresponding author Stephen Tapscott, M.D., Ph.D., a member of the Hutchinson Center's Human Biology Division. "The occasional 'bursts' of DUX4 are thought to be toxic to the muscle cells, which leads to muscle cell death and the muscular dystrophy."

Tapscott led the study in collaboration with Daniel Miller, M.D., Ph.D., at the University of Washington, and co-authors Silvere van der Maarel, Ph.D., and Rabi Tawil, M.D., at Leiden University Medical Center and the Fields Center for FSHD and Neuromuscular Research at the University of Rochester, respectively.

Previously, these same investigators had shown that the reason some people are protected from getting FSHD is that they have mutations in a region of DNA that is necessary to stabilize the DUX4 gene product. These new findings confirm the role of the DUX4 protein in FSHD and reveal a new mechanism of human disease caused by the inefficient suppression of a retrogene that has a role in early development. These findings will provide a focus for future development of therapies for FSHD.

There are broader implications of the new research for understanding human evolution as well. Maintenance of a functional retrogene in humans indicates that it provided some selective advantage during evolution.

"Since FSHD is characterized by excessively weak upper extremity muscles and facial muscles, we speculate that the DUX4 retrogene might have a normal role in causing the weaker and more expressive facial muscles in humans compared to non-human primates," Tapscott said. "If this suggestion is correct, it means that FSHD is caused by increasing the normal role of DUX4 and causing a more extreme weakness of facial and upper extremity muscles. It also means that all humans have a little bit of FSHD and that this contributes to the evolution of these muscles."

The researchers have an ongoing collaboration through a Hutchinson Center-based National Institutes of Health FSHD Program Project Grant, of which Tapscott is principal investigator, and through the Fields Center for FSHD and Neuromuscular Research, of which Tawil is the director.

"The progress was made possible by an unusual degree of collaboration and data-sharing among the individual groups," Tapscott said.

Grants from the NIAMS and NINDS sections of the National Institutes of Health, the Friends of FSH Research, the Shaw Family Foundation and the Muscular Dystrophy Association also supported the work of Tapscott and colleagues at the Hutchinson Center.

Other funding for this study came from the Fields Center, the Netherlands Organization for Scientific Research, the Netherlands Genomic Initiative, a Marjorie Bronfman Fellowship grant from the FSH Society, the Centro Investigacion Biomedica en Red para Enfermedades Neurodegenerativas, the Basque Government and the Instituto Carlos III, ILUNDAIN Fundazioa.


Story Source:

The above story is based on materials provided by Fred Hutchinson Cancer Research Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lauren Snider, Linda N Geng, Richard J L F Lemmers, Michael Kyba, Carol B Ware, Angelique M Nelson, Rabi Tawil, Galina N Filippova, Silvθre M van der Maarel, Stephen J Tapscott, Daniel G Miller. Facioscapulohumeral Dystrophy: Incomplete Suppression of a Retrotransposed Gene. PLoS Genetics, 2010; DOI: 10.1371/journal.pgen.1001181

Cite This Page:

Fred Hutchinson Cancer Research Center. "Uncovering the cause of a common form of muscular dystrophy: Research team makes second critical advance." ScienceDaily. ScienceDaily, 28 October 2010. <www.sciencedaily.com/releases/2010/10/101028174550.htm>.
Fred Hutchinson Cancer Research Center. (2010, October 28). Uncovering the cause of a common form of muscular dystrophy: Research team makes second critical advance. ScienceDaily. Retrieved April 18, 2015 from www.sciencedaily.com/releases/2010/10/101028174550.htm
Fred Hutchinson Cancer Research Center. "Uncovering the cause of a common form of muscular dystrophy: Research team makes second critical advance." ScienceDaily. www.sciencedaily.com/releases/2010/10/101028174550.htm (accessed April 18, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, April 18, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Our Love Of Puppy Dog Eyes Explained By Science

Our Love Of Puppy Dog Eyes Explained By Science

Newsy (Apr. 17, 2015) — Researchers found a spike in oxytocin occurs in both humans and dogs when they gaze into each other&apos;s eyes. Video provided by Newsy
Powered by NewsLook.com
Dr. Oz Under Fire For 'Quack Treatments' Yet Again

Dr. Oz Under Fire For 'Quack Treatments' Yet Again

Newsy (Apr. 17, 2015) — Ten doctors signed a letter urging Columbia University to drop Dr. Oz as vice chair of its department of surgery, saying he plugs "quack" treatments. Video provided by Newsy
Powered by NewsLook.com
Scientists Find Link Between Gestational Diabetes And Autism

Scientists Find Link Between Gestational Diabetes And Autism

Newsy (Apr. 17, 2015) — Researchers who analyzed data from over 300,000 kids and their mothers say they&apos;ve found a link between gestational diabetes and autism. Video provided by Newsy
Powered by NewsLook.com
Video Messages Help Reassure Dementia Patients

Video Messages Help Reassure Dementia Patients

AP (Apr. 17, 2015) — Family members are prerecording messages as part of a unique pilot program at the Hebrew Home in New York. The videos are trying to help victims of Alzheimer&apos;s disease and other forms of dementia break through the morning fog of forgetfulness. (April 17) Video provided by AP
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

 

Health & Medicine

Mind & Brain

Living & Well

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