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.
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.
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 i
|Contact: Anne Rueter|
University of Michigan Health System