DNA Testing for Type III von Willebrand Disease in Dutch Kooiker Dogs

Abstract

Von Willebrand disease type III is widespread in Dutch Kooiker dogs. To eradicate von Willebrand disease from the breed, affected dogs and nonsymptomatic carriers must be excluded from breeding. Previous efforts to detect carriers in Kooiker dogs by a von Willebrand factor antigen assay were not satisfactory because of considerable overlap of plasma concentrations in normal dogs and carriers. The aim of this study was to develop and apply a DNA test for the detection of von Willebrand disease carriers in the Kooiker breed. Two mutations in the von Willebrand factor gene in affected Kooiker dogs have been described previously, a splice site mutation at the border of intron 16 and exon 16 and a missense mutation in exon 3. We have developed polymerase chain reaction tests for both mutations in genomic DNA. The missense mutation most likely is a neutral variant and appears to be a polymorphism present in many breeds. The allele-specific oligonucleotide test for the splice site mutation was applied in the selection of animals cleared to breed by the Dutch breeding club. In a few years, the mutation has been eliminated from the breeding stock without apparent increase of inbreeding or preferential sire usage.

vWDI is inherited in an autosomal dominant manner with incomplete penetrance, in the Kromfohrländer breed

“…This second variant possibly acts in concert with the long thought causative vWDII mutation to cause the bleeding disorder in the Pointer breeds. Type III is rare in dogs as well and only found in Scottish Terriers [7, 8], Shetland Sheepdogs [7, 9], Kooikerhondje [10, 11] and Chesapeake Bay Retriever [12]. This is the most severe form of vWD with no detectable amount of vWF in plasma [13].…”