Featured Research

from universities, journals, and other organizations

Next generation sequencing establishes genetic link between two rare diseases

Date:
August 1, 2010
Source:
Cell Press
Summary:
Scientists have successfully used "next generation sequencing" to identify mutations that may cause a rare and mysterious genetic disorder. The research demonstrates that sequencing an affected individual's entire "exome"; that is, all of the genes that carry instructions for producing proteins, can reveal critical genes that when mutant, cause inherited disorders.

Scientists have successfully used "next generation sequencing" to identify mutations that may cause a rare and mysterious genetic disorder. The research, published on July 29th in the American Journal of Human Genetics, demonstrates that sequencing an affected individual's entire "exome"; that is, all of the genes that carry instructions for producing proteins, can reveal critical genes that when mutant, cause inherited disorders.

Perrault syndrome is a recessive disorder that is associated with hearing loss in both boys and girls, and failure of ovarian function in girls. Some individuals with Perrault syndrome also have neurological symptoms. Prior to the current study, no genes for Perrault syndrome had been identified.

A research group led by Mary-Claire King, PhD, from the University of Washington in Seattle studied the genetics of Perrault syndrome in a small family, originally of Irish and Italian ancestry, that included two sisters with well-characterized Perrault syndrome.

"Because the family is small and not consanguineous (both parents descended from a common ancestor), standard genetic mapping techniques would not have been informative in identifying the responsible gene," explains Dr. King. "Instead, we attempted to identify the gene responsible for Perrault syndrome in this family through the use of whole exome sequencing." The exome can be thought of as a kind of genetic blueprint for the synthesis of proteins.

After sequencing the entire exome of one of the sisters, the researchers identified a single gene (HSD17B4) that exhibited two rare functional variants. This gene encodes D-bifunctional protein (DBP), a multifunctional enzyme involved in lipid metabolism. Underscoring the genetic diversity of the disease, the researchers went on to show that six other families with Perrault syndrome had normal HSD17B4.

"Other mutations in HSD17B4 are known to cause a very severe congenital syndrome called DBP deficiency that is generally fatal within the first two years of life," says Dr. King. "No girls with DBP deficiency have been reported to survive past puberty, so ovarian abnormalities have not previously been known to be associated with this illness. The few reported long term survivors of DBP deficiency exhibit hearing loss and neurological dysfunction."

Taken together, the findings indicate that Perrault syndrome and DBP deficiency share some clinical symptoms and that very mild cases of DBP deficiency may be under-diagnosed. "Our research also demonstrates that whole exome sequencing can reveal critical genes in small nonconsanguinous families," concludes Dr. King.

The researchers include Sarah B. Pierce, University of Washington, Seattle, WA; Tom Walsh, University of Washington, Seattle, WA; Karen M. Chisholm, University of Washington, Seattle, WA; Ming K. Lee, University of Washington, Seattle, WA; Anne M. Thornton, University of Washington, Seattle, WA; Agata Fiumara, University of Catania, Catania, Italy; John M. Opitz, University of Utah School of Medicine, Salt Lake City, UT; Ephrat Levy-Lahad, Shaare Zedek Medical Center, Jerusalem, Israel, Hebrew University Medical School, Jerusalem, Israel; Rachel E. Klevit, University of Washington, Seattle WA; and Mary-Claire King, University of Washington, Seattle, WA.


Story Source:

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


Cite This Page:

Cell Press. "Next generation sequencing establishes genetic link between two rare diseases." ScienceDaily. ScienceDaily, 1 August 2010. <www.sciencedaily.com/releases/2010/07/100729122322.htm>.
Cell Press. (2010, August 1). Next generation sequencing establishes genetic link between two rare diseases. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2010/07/100729122322.htm
Cell Press. "Next generation sequencing establishes genetic link between two rare diseases." ScienceDaily. www.sciencedaily.com/releases/2010/07/100729122322.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
Powered by NewsLook.com
Google's Next Frontier: The Human Body

Google's Next Frontier: The Human Body

Newsy (July 27, 2014) Google is collecting genetic and molecular information to paint a picture of the perfectly healthy human. Video provided by Newsy
Powered by NewsLook.com
What's To Blame For Worst Ebola Outbreak In History?

What's To Blame For Worst Ebola Outbreak In History?

Newsy (July 27, 2014) A U.S. doctor has tested positive for the deadly Ebola virus, as the worst-ever outbreak continues to grow. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. 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