Mutation in HSF4 is Associated with Hereditary Cataract in the Australian Shepherd
Tufts' Canine and Feline Breeding and Genetics Conference, 2007
Cathryn Mellersh; Bryan McLaughlin; Louise Pettitt; Keith Barnett
Animal Health Trust
Newmarket, Suffolk, UK


Cataract is recognised as one of the most frequent intraocular diseases and a leading cause of blindness in the dog. The classification of canine cataract may depend upon the cause; their anatomical position in the lens; the progressive or stationary nature; and the presence or absence of another ocular disease. Canine cataract may also be classified as hereditary or non-hereditary; the former usually exhibiting marked breed specificity in their ophthalmoscopic appearance, age of onset, rate of progression and degree of bilateral symmetry; the latter generally do not exhibit any breed specificity. Primary HC has been described in as many as 97 different breeds with some breeds, such as the Boston Terrier, displaying more than one form.

Previously we identified a mutation in HSF4 that causes hereditary cataract (HC) in the Staffordshire bull terrier, the Boston terrier and the French Bulldog. The mutation, that causes a recessive, early-onset, rapidly progressive form of HC in these breeds is a single C nucleotide deletion in exon 9 that generates a frame shift and a premature stop codon. The C insertion occurs in a homopolymer run of 10 C nucleotides. We also identified a similar mutation in the Australian Shepherd (AS); the mutation in this breed is a single C nucleotide insertion in the same run of C's and also causes a frame shift and a premature stop codon, 177 nucleotides (59 amino acids) further downstream from that introduced by the deletion. In our initial studies we found 7 out of 7 ASs with cataracts carried the HSF4 deletion and that 6 out of the 7 were heterozygous for the mutation, indicating the condition might be dominant in this breed.

Since our initial studies we have collected DNA samples from 165 ASs, each of which has been examined by a veterinary ophthalmologist. 82 dogs have been diagnosed as suffering from a cataract of some kind and 58 have bilateral cataracts, the majority of which are posterior polar cataracts. We have genotyped all 165 dogs for the HSF4 insertion; 53 (67%) dogs with cataracts (all types) are either homozygous or heterozygous for the mutation and 46 (79%) dogs with bilateral cataracts carry the mutation. 72 (84%) dogs that are clear of cataracts are homozygous for the wild type HSF4 allele. These results indicate a significant association (p<0.001) between this HSF4 mutation and cataracts in the AS.

The majority of dogs (62%) with bilateral cataracts that carry the HSF4 mutation are heterozygous for the mutation, indicating the condition is dominant, or co-dominant in this breed. We also observe a wide variation in the age of onset of HC in the AS. The average age of onset for dogs that are homozygous for the mutation (-/-) is 3.55 years of age (std 2.20, min 0.24, max 6.91), whereas for the heterozygous dogs (+/-) the average age of onset is 5.51 (std 2.85, min 1.13, max 12.30). Reasons for the wide variation are currently under investigation.

A DNA test for HC in the Australian Shepherd will shortly be offered by the Animal Health Trust and will enable breeders to make progress eliminating HC from the AS. Because HC appears to be a dominant or co-dominant condition in this breed the advice will be to avoid breeding with all dogs that carry the mutation, until the factors influencing age of onset are better understood. The good news for breeders is that some dogs that are clear of the mutation but that are currently excluded from breeding, because they have produced affected offspring, can be returned to the breeding population.

Speaker Information
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Cathryn Mellersh
Animal Health Trust
Newmarket, Suffolk, UK

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