Navigation Links
Causative gene of a rare disorder discovered by sequencing only protein-coding regions of genome
Date:11/19/2009

For the first time, scientists have successfully used a method called exome sequencing to quickly discover a previously unknown gene responsible for a mendelian disorder.

Mendelian disorders, such as cystic fibrosis and sickle cell disease, are the result of one or more mutations in a single gene, typically a gene that makes a protein. All of the regions that code for proteins taken together are called the exome. The exome makes up about 1 percent of the genome, but it is in this 1 percent that more than 85 percent of mutations that cause mendelian disorders are found. That is why sequencing the exome is an efficient strategy to search for genes that underlie rare genetic disorders.

The study, "Exome sequencing identifies the cause of a mendelian disorder," was led by University of Washington (UW) researchers and published Nov. 13 in Nature Genetics.

While most mendelian disorders are rare, there are 7,000-plus suspected mendelian disorders that in aggregate affect millions of people in the United States, according to Dr. Michael J. Bamshad, one of the senior authors of the study, a UW professor of genome sciences and pediatrics, and a pediatrician at Seattle Children's. "Our results show that scientists could use exome sequencing to identify the genetic cause for thousands of disorders for which the gene hasn't been discovered."

"One of the reasons that this strategy is so powerful is that the scientists need only use a small number of unrelated cases to find the gene," said the other senior author of the study, Dr. Jay Shendure, UW assistant professor of genome sciences.

Dr. James Kiley, director of the Division of Lung Diseases at the National Heart, Lung and Blood Institute, part of the National Institutes of Healths in Bethesda, Md., said, "Following the recent successes with genome-wide association studies, this promising technology will advance our understanding of the genetic variants of both common disorders and rare diseases."

The disorder the UW research team used to test the strategy is Miller syndrome, whose genetic cause had been impossible to determine through conventional approaches. People with this syndrome have a number of malformations affecting their mouths, eyelids, ears, and feet. The research team was able to find that mutations in the gene, DHODH, cause Miller syndrome.

"Identifying the genetic basis of rare, single-gene diseases is of substantial interest to medical scientists," said Sarah Ng, a UW genome sciences graduate student and co-first author of the study, "because it provides important knowledge about disease mechanisms, biological pathways, and potential targets for therapies."

"Once we discover the causative gene," she added, "we can begin to look at how the gene might lead to the development of disease and what factors predict the outcome."

After scientists identify one causative gene and its repercussions, by extension they might discover other genes or environmental agents that affect the same biological pathway. For example, the malformation patterns found in Miller syndrome are similar to the birth defects in fetuses of some, but not all, mothers who took the drug methotrexate during pregnancy. Knowing this might provide some clues to genetic susceptibility to birth defects from methotrexate.

The ability of exome sequencing to identify a causative gene in a few months, compared to earlier methods that took years, "caused an audible gasp in the audience when we presented these findings to our peers," Bamshad said. "The power of this strategy is remarkable to many of us."

"We hope that the results of this study help point the way for thousands of scientists working on rare disorders who are seeking more efficient ways to locate the causative gene," Shendure added. "The exome sequencing strategy may also prove useful in studies of common disorders with complex genetics."


'/>"/>

Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert  

Related biology news :

1. Depression and anxiety disorders of adolescents are not the same thing
2. Are the monoamines involved in shaping conduct disorders?
3. Fighting the burden of mental disorders
4. Researchers restore missing protein in rare genetic brain disorder
5. Researchers report gene associated with language, speech and reading disorders
6. Severe breathing disorders during sleep are associated with an increased risk of dying
7. UGA researchers propose model for disorders caused by improper transmission of chromosomes
8. Abnormal brain circuits may prevent movement disorder
9. U of M study identifies risk factors of disordered eating in overweight youth
10. New research finds possible genetic link to cause of pregnancy loss and disorders
11. Scripps Research scientists observe human neurodegenerative disorder in fruit flies
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Causative gene of a rare disorder discovered by sequencing only protein-coding regions of genome
(Date:5/6/2017)... -- RAM Group , Singaporean based technology ... biometric authentication based on a novel  quantum-state ... perform biometric authentication. These new sensors are based on a ... Group and its partners. This sensor will have widespread ... security. Ram Group is a next generation sensor ...
(Date:4/19/2017)... 2017 The global military biometrics ... marked by the presence of several large global players. ... five major players - 3M Cogent, NEC Corporation, M2SYS ... nearly 61% of the global military biometric market in ... global military biometrics market boast global presence, which has ...
(Date:4/17/2017)... -- NXT-ID, Inc. (NASDAQ: NXTD ) ("NXT-ID" or ... 2016 Annual Report on Form 10-K on Thursday April 13, 2017 ... ... Investor Relations section of the Company,s website at http://www.nxt-id.com  under ... http://www.sec.gov . 2016 Year Highlights: ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... AMRI, ... and biotechnology industries to improve patient outcomes and quality of life, will now ... testing are being attributed to new regulatory requirements for all new drug products, ...
(Date:10/11/2017)... NJ (PRWEB) , ... October 11, 2017 , ... Personal eye wash is a basic ... one eye at a time. So which eye do you rinse first if a dangerous ... have Plum Duo Eye Wash with its unique dual eye piece. , “Whether ...
(Date:10/11/2017)... Netherlands and LAGUNA HILLS, Calif. ... Institute of Cancer Research, London (ICR) ... MMprofilerâ„¢ with SKY92, SkylineDx,s prognostic tool to risk-stratify patients with ... known as MUK nine . The University of ... which is partly funded by Myeloma UK, and ICR will ...
(Date:10/10/2017)... (PRWEB) , ... October 10, 2017 , ... San Diego-based ... of its corporate rebranding initiative announced today. The bold new look is part ... as the company moves into a significant growth period. , It will also expand ...
Breaking Biology Technology: