Gene scan helps identify cause of inherited blindness

September 7, 2010 By Michael C. Purdy

(PhysOrg.com) -- Scientists at Washington University School of Medicine in St. Louis have scanned the entire genome of mice for genes that help build photoreceptors, the light-sensing cells of the eye.

The results have already helped researchers identify the gene that causes a form of retinitis pigmentosa, a type of inherited blindness in humans.

"Quite a few of the more than 160 linked to blindness are active in ," says Joseph Corbo, MD, PhD, assistant professor of pathology and immunology. "There are many of these still left to be discovered, and when we find patients whose blindness can't be explained by genes we already know about, this new dataset can serve as a pointer to the best places to look."

Results of the gene scan appear this month in Genome Research; the identification of the retinitis pigmentosa gene is detailed in a separate paper published last month in The .

Corbo's lab and collaborator Thomas Langmann, PhD, of the Institute of Human Genetics in Regensburg, Germany, conducted the scan by looking for regions on mouse DNA that can bind to CRX, a protein that turns genes on or off in photoreceptors. They found CRX binding sites near many of the genes already known to be involved in photoreceptor development as well as hundreds of additional genes.

According to Corbo, the results indicate that CRX is a more important driver of photoreceptor development than researchers realized.

"We knew it was a key regulator, but we didn't realize the extent of its influence," he says. "It seems to have binding sites around almost every photoreceptor gene."

In a second study, researchers applied the scan results to genetic data from a family with an unexplained form of . Previous studies had determined that the problem in this family lies in a region of DNA containing 134 genes. Researchers used CRX binding to pinpoint a gene called FAM161A as the cause of blindness in this family.

"The CRX binding results allowed us to rapidly prioritize which of the 134 genes in this region were likely to be causing the disease." Corbo explains. "I think this is going to be widely applicable in the hunt for other genes, which is important because finding the causative gene is a necessary step toward developing effective therapies for individual patients."

More information: -- Corbo JC, Lawrence KA, Karlstetter M, Myers CA, Abdelaziz M, Dirkes W, Weigelt K, Seifert M, Benes V, Fritsche LG, Weber BHF, Langmann T. CRX ChIP-seq reveals the cis-regulatory architecture of mouse photoreceptors. Genome Research, online Aug. 6, 2010.

-- Langmann T, Di Gioia SA, Rau I, Stöhr H, Maksimovic NS, Corbo JC, Renner AB, Zrenner E, Kumaramanickavel G, Karlstetter M, Arsenijevic Y, Weber BHF, Gal A, Rivolta C. Nonsense mutations in FAM161A cause RP28-associated recessive retinitis pigmentosa. The American Journal of Human Genetics (2010), doi:10.1016/j.ajhg.2010.07.018

Related Stories

Recommended for you

Association found between abnormal cerebral connectivity and variability in the PPARG gene in developing preterm infants

December 12, 2017
(Medical Xpress)—A team of researchers with King's College London and the National Institute for Health Research Biomedical Research Centre, both in the U.K., has found what they describe as a strong association between ...

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.