Navigation Links
Fast-track gene-ID method speeds rare disease search
Date:9/16/2010

ANN ARBOR, Mich. A University of Michigan-led research team has identified a gene responsible in some families for a devastating inherited kidney disorder, thanks to a new, faster method of genetic analysis not available even two years ago. The success offers hope that scientists can speed the painstaking search for the genes responsible for many rare diseases and test drugs to treat them.

The U-M scientists report their success with exome capture, a groundbreaking genetic analysis technique, in the September issue of Nature Genetics.

The U-M- led international research team collaborated with two companies to test the emerging technology's ability to isolate the culprit gene in families with inherited single-gene kidney diseases. Many rare diseases that strike children and young adults result when a single gene malfunctions.

"We are one of the first research teams to take this technology and move it forward to identify single genes," says senior author Friedhelm Hildebrandt, M.D., a Howard Hughes Medical Institute Investigator, a Doris Duke Distinguished Clinical

Scientist and Frederick G. L. Huetwell Professor for the Cure and Prevention of Birth Defects at U-M.

"For us, it's a big leap in what genetics can do," Hildebrandt says. "In five years, families may be asked, 'Do you want to look at the cause of your rare disease?' In the not-too-distant future, we may be able to enroll them in a drug study."

Hildebrandt is an internationally known expert on the genetic basis of several severe kidney diseases that cause early renal failure in infants and children. He is also a professor in the U-M departments of human genetics and pediatrics and communicable diseases.

Hildebrandt and colleagues combined exome capture with a method of ultra-fast data analysis called massively parallel processing to identify a new gene involved in a family of congenital cystic kidney diseases known as nephronophthisis-related ciliopathies, or NPHP-RC. Taken together, these ciliopathy disorders are the most frequent genetically caused kidney disease in the first three decades of life.

The study results mean that Hildebrandt's team and other researchers now have an efficient way to identify yet-undiscovered genes involved in NPHP-RC disorders.

Hildebrandt's goal is to identify the genes responsible for these ciliopathies and find therapies to prevent or reverse their effects.

Research details

Hildebrandt used a combination of strategies of genetic analysis to expedite the search for the faulty gene in 10 NPHP-RC families. To screen candidate genes, the team collaborated with two companies, Roche NimbleGen, Inc., and Agilent, to apply the exome capture technique.

In the cell nucleus, exons, known collectively as the exome, are chains of nucleotides, or basic compounds that make up DNA, which leave the nucleus and produce proteins vital to body processes. Messenger RNA carries exons outside the nucleus, whereas other genetic material called introns remains behind. Capturing and analyzing only the exons speeded the search.

Context

People with NPHP-RC have abnormal development or degeneration of the kidneys, retina and cerebellum. Dialysis and kidney transplant are the only treatment options available.

The search for the genetic basis of these disorders, and other rare diseases as well, has turned out to be much more complicated than researchers hoped decades ago. Scientists have found that different single genes are responsible for disease in different subgroups of affected families. Discovering a culprit gene may yield insights for screening and future treatment, but only for a limited portion of all those affected.

Collaborating with scientists worldwide, Hildebrandt's lab has discovered more than 10 gene mutations that contribute to NPHP-RC diseases. But in an estimated 70 percent of cases, the gene involved is unknown.

What's next

"Once exome capture is used on a large scale, there will be databases that will reveal regions where mutations are known to cause disease," Hildebrandt says.

Future databases for rare diseases may take five to 10 years to develop. Testing of potential drug treatments can be expected to move forward at the same time. In zebrafish, Hildebrandt's lab has started to screen two drug compounds to see if either can restore the protein levels that the newly identified gene would produce if it functioned normally.


'/>"/>

Contact: Anne Rueter
arueter@umich.edu
734-764-2220
University of Michigan Health System
Source:Eurekalert

Related biology news :

1. New technique can fast-track better ionic liquids for biomass pre-treatments
2. OU study on genetics in fruit flies leads to new method for understanding brain function
3. New method successfully predicted how oil from Deepwater Horizon spill would spread
4. University at Buffalo symposium on in silico methods, high throughput screening
5. Cold Spring Harbor Protocols features chromosomal rearrangement, gene copy number methods
6. Half-a-loaf method can improve magnetic memories
7. Zinc finger nuclease, immunoprecipitation methods featured in Cold Spring Harbor Protocols
8. New methods, new math speed detection of drug-resistant malaria
9. Body of evidence: New fast, reliable method to detect gravesoil
10. California team to receive up to $122 million to develop method to produce fuels from sunlight
11. Mother Nature to provide an environmentally friendly method for reducing mosquitoes
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/31/2016)... BOCA RATON, Florida , March 31, 2016 /PRNewswire/ ... LEGX ) ("LegacyXChange" or the "Company") ... presentation for potential users of its soon to be ... The video ( https://www.youtube.com/channel/UCyTLBzmZogV1y2D6bDkBX5g ) will also ... by the use of DNA technology to an industry ...
(Date:3/22/2016)... OTTAWA, Ontario , PROVO ... 2016 Newborn Screening Ontario (NSO), which operates ... for molecular testing, and Tute Genomics and ... process management technology respectively, today announced the launch of ... new next-generation sequencing (NGS) testing panel. ...
(Date:3/15/2016)... Yissum Research Development Company of the Hebrew University ... University, announced today the formation of Neteera Technologies ... biological indicators. Neteera Technologies has completed its first round ... Neteera,s ... from sweat ducts, enables reliable and speedy biometric identification, ...
Breaking Biology News(10 mins):
(Date:5/3/2016)... ... May 03, 2016 , ... ... the sensor and data driven conferences, will take place on June 7-8, 2016, at the New ... Vidya Raman-Tangella on incorporating technology -- including AR/VR, machine learning, apps, robotics and AI ...
(Date:5/3/2016)... Los Angeles, Calif (PRWEB) , ... May 03, ... ... network of industry leading fertility clinics and IVF laboratories. A contingency of reproductive ... Fertility™ to treat men and women experiencing infertility and to help them build ...
(Date:5/2/2016)... ... May 02, 2016 , ... ... on the pre-launch success of their revolutionary, veterinarian-designed product for indoor cats. The ... trap, and play with their food the way nature intended. NoBowls make cats ...
(Date:4/29/2016)... 2016 According to a ... "Separation Systems for Commercial Biotechnology Market - Global ... 2015 - 2023", the separation systems for commercial ... in 2014 and is projected to expand at ... to reach US$ 19,227.8 Mn in 2023. ...
Breaking Biology Technology: