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Glaucoma Research Progress Summary

Canine glaucoma is a devastating disease that can not only lead to blindness, but is also very painful, often necessitating surgical removal of the eyes. A form of glaucoma that occurs in Bouvier des Flanders dogs has a hereditary basis. We are conducting studies to identify the mutation that causes this disease. We use an approach called whole genome sequence (WGS) analysis. Every dog has tens of thousands of genes and every gene is made up of a very long string of code letters in a precise order, much like a book is made up of paragraphs that are made up of strings of letters and spaces arranged in a specific order. Alterations of the code letters in a gene can result in the gene not working properly, much like changing a word in a sentence can change its meaning. With WGS, we can “read” the sequences of the code letters that make up every gene in a dog. We compare these sequences between affected and unaffected Bouviers to find variations in the code that occur in all of the dogs with glaucoma and none of the unaffected dogs. To date, we have collected samples from a key group of affected and unaffected dogs and generated WGS data from them. Using these data, we have ruled out certain types of changes in the genetic code that could underlie the disease. The changes we have ruled out are similar to changes in a sentence that consist of misspellings or deletions of single words. There are a number of other potential changes in the genetic code that we have not yet screened for. These changes are similar to such things as deleting a sentence from a paragraph or changing the order of sentences in a paragraph. We are working to analyze the WGS data to see whether any of these types of changes might underline Bouvier glaucoma. Our goal is to develop a simple genetic test that will enable dog breeders to screen for the genetic defect that causes Bouvier glaucoma so that they can avoid passing this defect to their offspring.