Navigation Links
CSHL scientists use next-gen sequencing to rapidly discover genetic cause of devastating disorder

Cold Spring Harbor, N.Y. 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.


Contact: Hema Bashyam
Cold Spring Harbor Laboratory

Related biology news :

1. UW-Madison scientists create super-strong collagen
2. Scientists find amazing new pondlife on nature reserve
3. New spider species discovered by University of Haifa scientists
4. Eminent group of scientists call for moratorium on issuance of mountaintop mining permits
5. CSHL scientists uncover role of protein critical for activating DNA replication
6. Scientists breakthrough in production of biofuels
7. Scientists create early-warning system to defend rare Jersey cows from continental disease
8. New discovery by Harvard scientists aims to correct cellular defects leading to diabetes
9. Scripps Florida scientists show lifeless prions capable of evolutionary change and adaptation
10. Tarantula venom-based MD therapy to be advanced by UB scientists biotech company
11. Rice scientists divide and conquer
Post Your Comments:
(Date:11/18/2015)... , November 18, 2015 ... has published a new market report titled  Gesture Recognition ... and Forecast, 2015 - 2021. According to the report, the global ... and is anticipated to reach US$29.1 bn by 2021, ... North America dominated the ...
(Date:11/16/2015)... 2015  Synaptics Inc. (NASDAQ: SYNA ), ... announced expansion of its TDDI product portfolio with ... and display driver integration (TDDI) solutions designed to ... TDDI products add to the previously-announced TD4300 ... resolution), and TD4322 (FHD resolution) solutions. All four ...
(Date:11/10/2015)... 2015  In this report, the biomarkers ... product, type, application, disease indication, and geography. ... are consumables, services, software. The type segments ... efficacy biomarkers, and validation biomarkers. The applications ... development, drug discovery and development, personalized medicine, ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... LUMPUR, Malaysia , Nov. 24, 2015 /PRNewswire/ ... global contract research organisation (CRO) market. The trend ... result in lower margins but higher volume share ... increased capacity and scale, however, margins in the ... Research Organisation (CRO) Market ( ), ...
(Date:11/24/2015)... 2015 /CNW/ - iCo Therapeutics ("iCo" or "the Company") ... for the quarter ended September 30, 2015. Amounts, ... and presented under International Financial Reporting Standards ("IFRS"). ... said Andrew Rae , President & CEO ... not only value enriching for this clinical program, ...
(Date:11/24/2015)...  Clintrax Global, Inc., a worldwide provider of clinical research services ... that the company has set a new quarterly earnings record in ... growth posted for Q3 of 2014 to Q3 of 2015.   ... , with the establishment of an Asia-Pacific ... United Kingdom and Mexico , ...
(Date:11/24/2015)... -- SHPG ) announced today that Jeff Poulton ... th Annual Healthcare Conference in New York City ... EST (1:30 p.m. GMT). --> SHPG ) announced today ... the Piper Jaffray 27 th Annual Healthcare Conference in ... 2015, at 8:30 a.m. EST (1:30 p.m. GMT). --> ...
Breaking Biology Technology: