title: Polymorphisms in canine platelet glycoproteins identify potential platelet antigens.
abstract: Human alloimmune thrombocytopenic conditions caused by exposure to a platelet-specific alloantigen include neonatal alloimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness. More than 30 platelet-specific alloantigens have been defined in the human platelet antigen (HPA) system; however, there is no previous information on canine platelet-specific alloantigens. Using the HPA system as a model, we evaluated the canine ITGB3, ITGA2B, and GP1BB genes encoding GPIIIa (β3), GPIIb (αIIb), and GPIbβ, respectively, which account for 21 of 27 HPA, to determine whether amino acid polymorphisms are present in the orthologous canine genes. A secondary objective was to perform a pilot study to assess possible association between specific alleles of these proteins and a diagnosis of idiopathic thrombocytopenic purpura (ITP) in dogs. By using genomic DNA from dogs of various breeds with and without ITP, sequencing of PCR products encompassing all coding regions and exon-intron boundaries for these 3 genes revealed 4 single-nucleotide polymorphisms in ITGA2B resulting in amino acid polymorphisms in the canine genome, 3 previously reported and 1 newly identified (Gly[GGG]/Arg[AGG] at amino acid position 576 of ITGA2B. Of 16 possible ITGA2B protein alleles resulting from unique combinations of the 4 polymorphic amino acids, 5 different protein isoforms were present in homozygous dogs and explain all of the genotype combinations in heterozygous dogs. There was no amino acid polymorphism or protein isoform that was specific for a particular breed or for the diagnosis of ITP.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. callan@vet.upenn.edu.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Callan
authors.forename: Petra
authors.initials: P
authors.lastname: Werner
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Mason
authors.forename: Geralyn M
authors.initials: GM
authors.lastname: Meny
authors.forename: Michael G
authors.initials: MG
authors.lastname: Raducha
authors.forename: Paula S
authors.initials: PS
authors.lastname: Henthorn
mesh_terms: D000818:Animals; D016824:Antigens, Human Platelet; D001792:Blood Platelets / Q000276:immunology*; D004285:Dogs / Q000235:genetics*; D039421:Integrin alpha2 / Q000737:chemistry / Q000235:genetics; D039661:Integrin beta3 / Q000737:chemistry / Q000235:genetics; D007519:Isoantigens / Q000235:genetics*; D010865:Pilot Projects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000235:genetics; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D017422:Sequence Analysis, DNA
chemical_list: D016824:Antigens, Human Platelet; D039421:Integrin alpha2; D039661:Integrin beta3; D007519:Isoantigens; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins