Featured Research

from universities, journals, and other organizations

Fragile X protein linked to nearly 100 genes involved in autism

Date:
December 12, 2012
Source:
Duke University Medical Center
Summary:
Doctors have known for many years that patients with fragile X syndrome, the most common form of inherited intellectual disability, are often also diagnosed with autism. But little has been known about how the two diagnoses are related. Now scientists have pinpointed the precise genetic footprint that links the two.

Doctors have known for many years that patients with fragile X syndrome, the most common form of inherited intellectual disability, are often also diagnosed with autism. But little has been known about how the two diagnoses are related.

Now a collaborative research effort at Duke University Medical Center and Rockefeller University has pinpointed the precise genetic footprint that links the two. The findings, published online in the journal Nature on Dec. 12, 2012, point the way toward new genetic testing that could more precisely diagnose and categorize the spectrum of autism-related disorders.

Fragile X syndrome is the most well understood single-gene cause of autism. It results from defects on a small part of the genetic code for a protein that researchers have dubbed the fragile X mental retardation protein, or FMRP.

Normally, FMRP plays an important role controlling production of other proteins in the brain and other organs. It does this by looking for specific genetic patterns located on the messages encoding proteins. When it locates these genetic flags, it attaches to them and, along with other signals, controls where and when protein is made.

In fragile X syndrome, this process breaks down because a defect in the gene causes the body to produce too little, or in some cases, none of the FMRP protein. As a result, additional proteins it would normally regulate are made in the wrong place and at the wrong time. Until now, little was known about how this process worked in people with the autism.

Using a combination of laboratory experiments and advanced bioinformatics, the research team, led by Thomas Tuschl, PhD, a Howard Hughes Medical Institute investigator at Rockefeller University, and Uwe Ohler, PhD, an associate professor in Biostatistics and Bioinformatics at the Duke Institute for Genome Sciences & Policy, identified both the genetic flags that FMRP is looking for and the genes it targets.

The researchers discovered that FMRP directly controls at least 93 genes that have been independently linked to autism, as well as Angelman, Prader-Willi, Rett and other neurologic syndromes that have overlapping features with autism.

Additional research using a mouse model of fragile X syndrome revealed that the animals had abnormal protein production not only in the brain, but also in the ovary. The findings confirmed that the absence of FMRP protein causes ovarian insufficiency, which is common among women affected by fragile x syndrome.

"We now know not only which genes are linked to FMRP, but we can locate exactly where they interact," said Ohler. "Down the road, this finding could lead to more detailed genetic tests that take into account the subtle ways that genes get turned on and off."

Physicians who work with fragile X patients know that each patient's abilities and challenges are unique. Some individuals have almost no disability, while others have more severe physical and intellectual disabilities. Approximately 2 percent to 6 percent of children with autism are also diagnosed with fragile X and about one-third of fragile X patients also meet the criteria for autism.

The new discovery should now enable researchers to examine the common molecular pathways leading to all forms of autism. Identification of those pathways could also lead to more targeted treatments for both fragile x and autism.

"We can now look for changes in the FMRP binding sites of genes to identify potential new genetic links to autism-spectrum disorders," said Neelanjan Mukherjee, a Duke post-doctoral scientist who contributed to the research.

In addition to Ohler, Mukherjee and Tuschl, study authors include Manuel Ascano Jr., Pradeep Bandaru, Jason B. Miller, Jeff Nusbaum, David L. Corcoran, Christine Langlois, Mathias Munschauer, Scott Dewell, Markus Hafner and Zev Williams.

The study was funded with grants from the National Institutes of Health (UL1RR024143, R01MH080442), the Howard Hughes Medical Institute, Simons Foundation Autism Research Initiative, and the National Science Foundation. The research team recently received an NIH transformative research award (R01GM104962) that will enable the team to continue its investigation.


Story Source:

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


Journal Reference:

  1. Manuel Ascano, Neelanjan Mukherjee, Pradeep Bandaru, Jason B. Miller, Jeffrey D. Nusbaum, David L. Corcoran, Christine Langlois, Mathias Munschauer, Scott Dewell, Markus Hafner, Zev Williams, Uwe Ohler, Thomas Tuschl. FMRP targets distinct mRNA sequence elements to regulate protein expression. Nature, 2012; DOI: 10.1038/nature11737

Cite This Page:

Duke University Medical Center. "Fragile X protein linked to nearly 100 genes involved in autism." ScienceDaily. ScienceDaily, 12 December 2012. <www.sciencedaily.com/releases/2012/12/121212134052.htm>.
Duke University Medical Center. (2012, December 12). Fragile X protein linked to nearly 100 genes involved in autism. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2012/12/121212134052.htm
Duke University Medical Center. "Fragile X protein linked to nearly 100 genes involved in autism." ScienceDaily. www.sciencedaily.com/releases/2012/12/121212134052.htm (accessed October 20, 2014).

Share This



More Mind & Brain News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Court Ruling Means Kids' Online Activity Could Be On Parents

Court Ruling Means Kids' Online Activity Could Be On Parents

Newsy (Oct. 17, 2014) In a ruling attorneys for both sides agreed was a first of its kind, a Georgia appeals court said parents can be held liable for what kids put online. Video provided by Newsy
Powered by NewsLook.com
The Best Foods To Boost Your Mood

The Best Foods To Boost Your Mood

Buzz60 (Oct. 17, 2014) Feeling down? Reach for the refrigerator, not the medicine cabinet! TC Newman (@PurpleTCNewman) shares some of the best foods to boost your mood. Video provided by Buzz60
Powered by NewsLook.com
You Can Get Addicted To Google Glass, Apparently

You Can Get Addicted To Google Glass, Apparently

Newsy (Oct. 15, 2014) Researchers claim they’ve diagnosed the first example of the disorder in a 31-year-old U.S. Navy serviceman. Video provided by Newsy
Powered by NewsLook.com
First Confirmed Case Of Google Glass Addiction

First Confirmed Case Of Google Glass Addiction

Buzz60 (Oct. 15, 2014) A Google Glass user was treated for Internet Addiction Disorder caused from overuse of the device. Morgan Manousos (@MorganManousos) has the details on how many hours he spent wearing the glasses, and what his symptoms were. Video provided by Buzz60
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