Objective—To define the relationship between clinical
expression of a type-1 von Willebrand disease
phenotype and genotype at 2 von Willebrand factor
marker loci in Doberman Pinschers.
Animals—102 client-owned Doberman Pinschers.
Procedures—Dogs were recruited on the basis of
plasma von Willebrand factor concentration, clinical
history, and pedigree. Blood samples and response to
a history questionnaire were obtained for each dog.
Plasma von Willebrand factor concentration was measured
by use of an ELISA, and genotyping was performed
via polymerase chain reaction for 1 intragenic
and 1 extragenic von Willebrand factor marker.
Amplification product size was determined by use of
polyacrylamide gel electrophoresis (intragenic marker)
or automated sequence analysis (extragenic marker).
Western blots were prepared from a subset of
dogs with low plasma von Willebrand factor concentration
to evaluate multimer distribution.
Results—Strong associations were detected
between plasma von Willebrand factor concentration
and von Willebrand factor marker genotype. Twentyfive
dogs had substantial reduction in plasma von
Willebrand factor concentration and multiple hemorrhagic
events. All were homozygous for a 157-basepair
intragenic marker allele and homozygous or compound
heterozygous for 1 of 4 extragenic marker alleles.
These marker genotypes were exclusively
detected in dogs with low plasma von Willebrand factor
concentration, although some dogs with these
genotypes did not have abnormal bleeding.
Conclusions and Clinical Relevance—Type-1 von
Willebrand disease in Doberman Pinschers is associated
with the von Willebrand factor gene locus; however,
the expression pattern in this breed appears
more complex than that of a simple recessive trait.
(Am J Vet Res 2001;62:364–369)