Mutation in HSF4 is associated with hereditary cataract in the Australian Shepherd.

Cataracts are a leading cause of blindness in dogs with approximately 100 breeds affected by primary hereditary forms. Despite the large number of breeds affected with hereditary cataracts (HC) little is known about the genetics of the condition, and to date only a single gene, HSF4, has been implicated in the development of the disease in dogs. We previously identified a recessively inherited 1-bp insertion in the transcription factor gene HSF4 resulting in the loss of the open reading frame in Boston terriers and Staffordshire bull terriers. While testing the insertion mutation in other breeds with HC, we identified a 1-bp deletion at the same nucleotide of HSF4 in some Australian Shepherds with cataract. Using DNA samples from almost 400 privately owned Australian Shepherds we have investigated the association between the deletion mutation in HSF4 and cataracts in this breed. We conclude that the mutation is significantly associated with cataracts and that a dog carrying the mutation is approximately 17 times more likely to develop binocular cataracts than dogs that are clear of the mutation. The data also indicate that additional mutations associated with the development of cataracts are likely to be co-segregating in the Australian Shepherd population.