MyDogDNA genome-wide analysis identifies carriers of a known bleeding disorder in Finnish Hounds and Welsh Springer Spaniels

Canine disease genomics progresses quickly and academic research groups around the world have already discovered mutations underlying more than 160 genetic disorders and traits in different breeds. Until today, testing of the known canine diseases has been possible only with separately conducted single-gene tests. Genoscoper Laboratories has, as the first animal diagnostics laboratory in the world, developed a unique genetic panel testing and reporting concept to efficiently and economically test most of the known mutations at once. As a result, mutations in over 100 known canine inherited disorders can be tested simultaneously as a part of the MyDogDNA service. This gives a unique opportunity not only to perform a comprehensive genetic screening in breeds with many known mutations, but also to discover known mutations in breeds that have never been investigated for any or only for few mutations.

The MyDogDNA pilot study carried out by Genoscoper Laboratories revealed several new affected breeds for known mutations. The MyDogDNA research team now reports the discovery of the mutation causing Canine Factor VII Deficiency (cFVII), a bleeding disorder, in two additional breeds, Finnish Hounds and Welsh Springer Spaniels. This discovery has several implications for these breeds, including the need for follow-up studies.

In the limited pilot study sample, several carriers were identified in both breeds. Dog owners, breeders and Breed Clubs of Finnish Hounds and Welsh Springer Spaniels are therefore invited in further research that would help determine the prevalence of the cFVII mutation within the two breeds.

The MyDogDNA analysis includes several internal quality parameters to provide a highest-quality testing service. In addition, new discoveries are always confirmed with additional experiments using alternate gene technologies. Additional studies confirmed presence of cFVII mutation in Finnish Hounds and Welsh Springer Spaniels. The MyDogDNA database offers a unique way of monitoring the breed frequency of a mutation on a global and national level with prevalence being updated in real-time with each tested dog.

Canine Factor VII (cFVII) deficiency is a recessive bleeding disorder

Canine Factor VII is a mild to moderate bleeding disorder characterized by abnormal bleeding tendency. It is caused by a genetic deficiency in the F7 gene that encodes a coagulation factor protein crucial for initiation of the blood coagulation process. This condition typically goes unnoticed until trauma or surgery reveals prolonged bleeding in affected dogs. However, bruises and body cavity-, nose- or vaginal bleeding may also be observed. Clinical symptoms can be reduced by blood transfusions, or by recombinant FVII therapy, but long-term management is difficult.

Canine FVII Deficiency follows autosomal recessive inheritance, meaning that a dog needs to inherit the causative mutation from both its dam and sire to manifest the disease. The mutation causing cFVII Deficiency was originally discovered in Beagles, and it has been reported also in Airedale Terrier, Alaskan Klee Kai, Giant Schnauzer and Scottish Deerhound.

Follow-up studies needed to validate the impact of the cFVII mutation in new breeds

Discovery of the same mutation in two additional breeds, Finnish Hounds and Welsh Springer Spaniels, warrants additional follow-up studies. Because the consequences of a genetic mutation are not necessarily the same in every breed, the discovery of cFVII in these two additional breeds highlights the need for further research to validate the link between the mutation and its manifestation as bleeding disorder. Other genetic factors may influence the severity, onset and progression of the condition. Therefore, understanding of the clinical consequences of a mutation in individual breeds requires careful follow-up studies, and collaboration with breeders, researchers and veterinarians.

For the validation of the impact of a mutation within a breed, it is important to identify a number of genetically affected (homozygous) dogs, and investigate whether the particular mutation leads to a similar phenotype as described in the original breeds the mutation was characterized in. It is important to notice that a newly discovered mutation cannot be called a disease-causing mutation in the new breed before the validation procedure has been completed. For this very reason, the new discoveries are not reported in the results of the MyDogDNA analysis before the clinical validation has taken place. As with recessively inherited disorders in general, carriers should not be excluded from breeding to avoid unnecessary loss of genetic diversity. This is particularly important in situations like this, where the pathogenic effect of the mutation has not yet been confirmed.

The MyDogDNA research team has  adopted a protocol for new discoveries and always seeks professional collaboration for their validation. Breed Club representatives, breeders, researchers and veterinarians are contacted and informed about the discovery of genetically affected dogs, and dog owners are contacted for possible follow-up studies. Validation results will be reported separately.

New discoveries prove that panel testing adds up the knowledge of canine inherited disorders

The discovery of known mutations in novel breeds proves the power of a comprehensive panel testing of canine inherited disorders in any breed. Academic research behind the original discoveries is often limited by sample numbers and typically reports only one or two affected breeds. Therefore, it is not a major surprise that the mutations are found in additional breeds afterwards. Knowledge of mutation discoveries is important to avoid the enrichment of a rare condition, for example, through a popular sire or dam, in the new affected breeds.

The MyDogDNA testing service is designed to combine testing and research; it is currently the only available tool that enables panel screening of known mutations within breed and comprehensive reporting with an affordable cost for the dog owners, but at the same time it helps identify and follow-up on known mutations facilitating further research and broadening our knowledge of the disease prevalences in our dog breeds.