Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Causative gene of a rare disorder discovered by sequencing only protein-coding regions of genome

23.11.2009
Results show exome-sequencing might help identify genetic cause of thousands of disorders

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."

The study published in Nature Genetics was a collaborative effort among scientists from many disciplines and institutions. Other authors include co-first author Kati J. Buckingham, from the UW Department of Pediatrics; Choli Lee, UW Department of Genome Sciences; Abigail W. Bigham, UW Department of Pediatrics; Holly K. Tabor, UW Department of Pediatrics and the Treuman Center for Pediatric Bioethics at Seattle Children's; Karin M. Dent and Chad D. Huff from the University of Utah departments of pediatrics and human genetics, respectively; Paul T. Shannon of the Institute of Systems Biology in Seattle; Ethylin Wang Jabs of the Department of Genetics and Genome Sciences at Mount Sinai School of Medicine and the Department of Pediatrics at Johns Hopkins University, and Deborah Nickerson from the UW Department of Genome Sciences.

The research was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Health and Human Development, the National Human Genome Research Institute, and the Heart, Lung, and Blood Institute, all at the National Institutes of Health; the state of Washington Life Sciences Discovery Fund and the Washington Research Foundation.

Leila Gray | EurekAlert!
Further information:
http://www.washington.edu

More articles from Life Sciences:

nachricht Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>