title: Cosegregation of a factor VIII microsatellite marker with mild hemophilia A in Golden Retriever dogs.
abstract: Mild hemophilia A (factor VIII deficiency) was diagnosed in Golden Retrievers and pedigree studies were undertaken to test the cosegregation of an intragenic factor VIII marker with the disease phenotype. The study population consisted of 30 client-owned dogs (22 males and 8 females). Hemophilic males (n = 12) typically demonstrated prolonged bleeding after trauma or surgery rather than spontaneous hemorrhagic events. The affected males had a proportionate reduction in factor VIII coagulant activity (mean FVIII:C = 4%) and factor VIII protein concentration (mean FVIII:Ag = 3%). Twenty-five dogs (10 affected males, 8 clear males, 2 obligate carrier dams, and 5 suspect carrier daughters) were genotyped for a factor VIII microsatellite marker, with allele size assigned by an automated capillary electrophoresis system. Five distinct marker alleles were present in the study pedigree and a 300-base pair allele was found to segregate with the hemophilia A phenotype. The inheritance of the hemophilia-associated allele defined carrier status for 5 suspect daughters of obligate carrier dams. The limitations inherent to linkage analyses (i.e., lack of access to key family members and homozygosity at the marker locus) did not preclude carrier detection in this pedigree. We conclude that genotype analysis for the intragenic factor VIII marker can aid in control of canine hemophilia A through enhanced carrier detection.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, Comparative Coagulation Section, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. mbb9@cornell.edu
authors.forename: Marjory B
authors.initials: MB
authors.lastname: Brooks
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Barnas
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fremont
authors.forename: Jharna
authors.initials: J
authors.lastname: Ray
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005169:Factor VIII / Q000235:genetics*; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics / Q000662:veterinary*; D018895:Microsatellite Repeats / Q000235:genetics*; D010375:Pedigree
chemical_list: D005169:Factor VIII