U-M researchers prove power of emerging technology as they identify new gene involved in inherited pediatric kidney disease
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 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.
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.
"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.
Citation: Nature Genetics, September 2010