A large screen of mouse strains identifies hundreds of new genes linked to blindness and other vision disorders. Many of these genes are likely important in human vision, and the results could help identify new causes of hereditary blindness in patients. The work was published today in Nature Communications Biology.
"This is extremely valuable for people with hereditary eye disease," says senior author Ala Moshiri of the University of California, Davis. "The whole ophthalmic community is going to start using these data."
The results are the latest to come from the International Mouse Phenotyping Consortium, of which UC Davis's Mouse Biology Program is a founding member. The goal of the consortium is to identify a function for every gene in the mouse genome by creating lines of "knockout" mice that lack a single specific gene and screening them for their effects.
The team combed the consortium database for genes linked to eye and vision defects. They identified 347 genes, of which 86 were already established to be involved in eye disease or to be associated with vision in some way. Three-quarters of the genes were not previously known to cause eye disease in any species.
"In 2018, if someone has a form of hereditary blindness, we can identify the cause 50 to 75 percent of the time," Moshiri says. "In the remaining cases, we know the mutation is there but we don't know where to look. Now eye centers that do DNA sequencing can call back patients and screen them for these new genes."
While the mouse and human genomes clearly differ, most human genes have an analogous counterpart in mice. The UC Davis team is collaborating with eye centers at Baylor College of Medicine in Houston and the University of Iowa to check the newly identified mouse genes against their human equivalents.
The new genetic information could also enable new therapies for hereditary eye disease. In 2017, the FDA approved the first gene therapy for any disease—treating hereditary blindness caused by a defect in the retinal gene RPE65.
"We expect that more and more of these genetic diseases will be treatable," says Moshiri.