Featured Research

from universities, journals, and other organizations

Next-generation sequencing used to rapidly discover genetic cause of devastating disorder

Date:
January 14, 2010
Source:
Cold Spring Harbor Laboratory
Summary:
Scientists have discovered a genetic mutation that causes Joubert Syndrome, a devastating inherited neurological disorder. They identified this mutation using whole exome sequencing -- a rapid "next-gen" sequencing approach that minimizes time and cost. The mutation, which causes a single nucleotide change in the TMEM216 gene, has a high carrier rate of 1:92 among Ashkenazi Jews.

Two scientists from Cold Spring Harbor Laboratory (CSHL) are part of an international team that has discovered a genetic mutation that causes Joubert Syndrome. JBTS, as it is commonly called, is a devastating inherited neurological disease that is very rare in the general population but found relatively more often among Ashkenazi Jews.

The study was published in collaboration with Dor Yeshorim, a non-profit organization offering premarital genetic disease carrier-screening primarily to the Orthodox Jewish community, and with a research group led by Dr. Orly Elpeleg at Hebrew University Medical Center, Israel. It appears in the January 8th issue of the American Journal of Human Genetics.

The mutation, in a gene called TMEM216, causes a single letter of the DNA alphabet to be replaced by another. Individuals who carry the mutation in copies of the gene inherited from both parents develop diverse and devastating pathologies. These include malformation of a brain region, delay in development, poor muscle coordination, visual impairment and growth of extra digits.

"This discovery makes it possible to prevent JBTS within this population by screening individuals for the mutation," said CSHL Professor and HHMI investigator Greg Hannon, one of the authors of the study. At the request of families of patients with JBTS, the study was initiated by Dor Yeshorim, which has already made available screening for the JBTS mutation.

Participants who undergo genetic screening are not given the screen's results, only an identification number. When a couple considers marriage, both partners submit their identification numbers. If both are carriers of the mutation, they are deemed incompatible and are so informed. "Asymptomatic carriers will thus be able to avoid passing the condition to their future children unknowingly," says Hannon.

JBTS has previously been linked to mutations in nine genes, but none of these mutations were present in JBTS patients within the Ashkenazi Jewish population. To hunt for the causative mutation in this ethnic group, the scientists from Hebrew University Medical Center initially used traditional sequencing methods to comb through bits of DNA from 11 JBTS patients from eight families, four of whom had a common ancestor. The two CSHL scientists undertook a parallel effort using a "next-generation" sequencing approach.

Instead of sequencing the whole genome, the CSHL scientists obtained genetic material from two other JBTS patients -- a mother and daughter -- and used a powerful genome fractionation method developed at CSHL to sequence just the "exome," -- the collection of exons, which are the bits of the genome that actually encode proteins. Both approaches yielded the same result: the mutated TMEM216 gene.

"Exons make up just one percent of the genome, so the exome sequencing process is not only much more economical, but also produces results much faster," says Yaniv Erlich, a graduate student in the Hannon laboratory and co-author of the paper. It only took three weeks for the CSHL scientists to find the mutation as compared with many months required by more traditional methods.

Once the causative mutation was identified, the collaborators combined efforts to screen more than 2,700 anonymous participants in the study. This mass screen revealed the high carrier rate of 1:92 among the cohort. The prevalence of the TMEM216 mutation in the wider population remains to be determined.

Whole-exome sequencing has been gaining momentum over the past few years. "But this is one of the first few studies to use next-generation sequencing to identify a causative mutation underlying a rare genetic disease," says Erlich. The CSHL scientists plan to expand their exome sequencing efforts to screen for mutations that cause other rare as well as common genetic diseases.


Story Source:

The above story is based on materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


Journal Reference:

  1. Edvardson et al. Joubert Syndrome 2 (JBTS2) in Ashkenazi Jews Is Associated with a TMEM216 Mutation. The American Journal of Human Genetics, 2010; 86 (1): 93 DOI: 10.1016/j.ajhg.2009.12.007

Cite This Page:

Cold Spring Harbor Laboratory. "Next-generation sequencing used to rapidly discover genetic cause of devastating disorder." ScienceDaily. ScienceDaily, 14 January 2010. <www.sciencedaily.com/releases/2010/01/100113104253.htm>.
Cold Spring Harbor Laboratory. (2010, January 14). Next-generation sequencing used to rapidly discover genetic cause of devastating disorder. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2010/01/100113104253.htm
Cold Spring Harbor Laboratory. "Next-generation sequencing used to rapidly discover genetic cause of devastating disorder." ScienceDaily. www.sciencedaily.com/releases/2010/01/100113104253.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deadly Ebola Virus Threatens West Africa

Deadly Ebola Virus Threatens West Africa

AP (July 28, 2014) West African nations and international health organizations are working to contain the largest Ebola outbreak in history. It's one of the deadliest diseases known to man, but the CDC says it's unlikely to spread in the U.S. (July 28) Video provided by AP
Powered by NewsLook.com
$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Two Americans Contract Ebola in Liberia

Two Americans Contract Ebola in Liberia

Reuters - US Online Video (July 28, 2014) Two American aid workers in Liberia test positive for Ebola while working to combat the deadliest outbreak of the virus ever. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) 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:
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