A von Willebrand's Factor Genomic Nucleotide Variant and Polymerase Chain Reaction Diagnostic Test Associated with Inheritable Type-2 von Willebrand's Disease in a Line of German Shorthaired Pointer Dogs

Abstract

Heritable, type-2 von Willebrand's disease (vWD) was studied in a line of German Shorthaired Pointers (GSPs) in which some members had a nucleotide variant in exon 28 of the von Willebrand factor (VWF) gene. A polymerase chain reaction (PCR) diagnostic test for the nucleotide variant was developed to establish the disorder's mode of inheritance and to eliminate it from the line. Thirty-six of the 49 GSPs in the line, 14 unrelated GSP controls, and 71 unrelated dogs of various breeds were tested for the presence of the variant nucleotide. All the dogs with a vWF antigen deficiency (<70% of normal) were either homozygous or heterozygous for the nucleotide variant. The variant was not located in any tested dog in the line or outside of the line with a vWF antigen value greater than 68%. Of the GSPs in the line tested, two were homozygous for the variant, 15 were heterozygous, and 19 were variant free. The collective evidence of this and other studies is consistent with the variant nucleotide being the cause of the type-2 vWD in this line of GSPs and German Wirehaired Pointers. The PCR diagnostic test for the variant nucleotide was successfully used to select and produce progeny that were variant free and vWD free. This test should be effective in the subsequent elimination of this same variant from other lines of dogs.

Köpeklerde von Willebrand Faktör Antijen Seviyesi ve von Willebrand Faktör Geni Arasındaki İlişkinin Belirlenmesi

“…In the present study; vWF: Ag concentration <50% individuals were considered to be vWD positive as reported by Burges et al [2] and Thomas [15] . Von Willebrand's disease is an acquired or inherited bleeding disorder common in humans and dogs [3] . In human beings estimated prevalence of vWD has been reported between 0.01-0.02% [9,16] .…”

“…Von Willebrand's disease (vWD) is the commonest an acquired or inherited bleeding disorders of dogs and humans being [1][2][3] .…”

“…Von Willebrand syndrome is transferred as autosomal recessive character in dogs [4] . The quantitative deficiencies or qualitative abnormalities of the von Willebrand's factor (vWF) or both causes bleeding tendency at the patients suffers from vWD [1,3] . The vWD phenotype can be classified as type I, II, and III on the basis of the plasma vWF concentration and the vWF multimer structure [1,2] .…”

“…It is reported that vWD is negative in dogs with vWF: Ag concentration >70% and is positive in dogs with vWF: Ag concentration <50% [2,5] . At the nucleotide sequences of von Willebrand factor gene (VWF) is determined to be 85% identical of human and canine and can be used as cross-species modelling of their vWDs [3] . The human VWF is located near the telomere of the short arm of chromosome 12 and split into 52 exons, spanning 180 kb of deoxyribonucleic acid [3] .…”

“…At the nucleotide sequences of von Willebrand factor gene (VWF) is determined to be 85% identical of human and canine and can be used as cross-species modelling of their vWDs [3] . The human VWF is located near the telomere of the short arm of chromosome 12 and split into 52 exons, spanning 180 kb of deoxyribonucleic acid [3] . In dogs; VWF has 178 kb size, and is in dog caryotype on number 12 chromosome, which has multiple repeated regions [6] .…”