title: Canine leukocyte adhesion deficiency: presence of the Cys36Ser beta-2 integrin mutation in an affected US Irish Setter cross-breed dog and in US Irish Red and White Setters.
abstract: Canine leukocyte adhesion deficiency (CLAD) is a primary immunodeficiency disease characterized by recurrent bacterial infections in the presence of marked leukocytosis. The disease was 1st described in the mid-1980s in a cross-breed Irish Setter Dog in the United States. It results from a defective beta-2 subunit of heterodimeric leukocyte adhesion proteins. The causative mutation for CLAD in Irish Setter Dogs from Europe has been identified as a missense mutation at base pair position 107 in the beta-2 integrin subunit gene (ITGB2) that results in an amino acid change from cysteine to serine at amino acid 36 (Cys36Ser) in the beta-2 integrin subunit protein. In the current work, the originally described dog with CLAD has been genetically tested and shown to have the same mutation as the European Irish Setters. This suggests that the mutation has been in the Irish Setter population for many generations spanning more than 2 decades. A related breed, the Irish Red and White Setter, has a history of interbreeding with Irish Setters and shares a common ancestry with the Irish Setter breed. DNA from Irish Red and White Setters residing in the United States was screened either by sequencing or by the newly developed restriction enzyme test for the Irish Setter Cys36Ser CLAD mutation. Seven of 54 dogs tested (13%) were found to be carriers of the Irish Setter CLAD mutation. Five of these were directly related to a sire from the UK, demonstrating the importation of an allele from another continent and establishing the need for genetic testing in this breed in the United States.
mesh_terms: D000818:Animals; D001483:Base Sequence; D001947:Breeding; D018821:CD18 Antigens / Q000235:genetics*; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000145:classification* / Q000235:genetics*; D005260:Female; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics* / Q000662:veterinary*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D014481:United States
chemical_list: D018821:CD18 Antigens