Researchers have discovered hundreds of new genes linked to blindness and other vision disorders in a screen of mouse strains.
Many of these genes are likely important in human eye vision and the results could help identify new causes of hereditary blindness in patients.
“This is extremely valuable for people with hereditary eye disease,” says Ala Moshiri, associate professor of ophthalmology and vision science in the School of Medicine and Eye Center at 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. 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. Consortium researchers have previously identified a set of genes essential to life, genes linked to deafness, and even those linked to hereditary bad breath.
To date, the consortium has generated more than 7,000 strains of gene-knockout mice, of which 4,364 have been characterized across 11 organ systems.
“The data being generated by the IMPC is accelerating the application of genomics in clinical medicine,” says Kent Lloyd, director of the Mouse Biology Program at UC Davis and principal investigator of the Knockout Mouse Production and Phenotyping (KOMP2) project at the university.
The team combed the consortium database for genes linked to eye and vision defects. They identified 347 genes, of which 86 were either well-established as involved in eye disease or were associated with vision in some way. Three-quarters of the genes—261—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,” says Moshiri. “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 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, Moshiri says.
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,” Moshiri says.
The work appears in Nature Communications Biology. Additional coauthors come from UC Davis and institutions around the world.
The National Institutes of Health, National Eye Institute, and the Medical Research Council in the UK funded the research. Additional support came from Research for Preventing Blindness, the International Retinal Research Foundation, and the government of Canada.
Source: UC Davis