CANINE MAJOR HISTOCOMPATIBILITY COMPLEX GENES DQA AND DQB IN IRISH-SETTER DOGS

Information about genetic variation within the canine major histocompa tibility complex (MHC) class II genes is limited. In common with most other vertebrate species the canine MHC, or DLA, includes genes which are homologous to human DR, DQ, and DP. Recently, at least one functio nal DLA DQ gene-pair has been characterized, but so far systematic scr eening efforts have been lacking. In the present study, we sequenced b oth cDNA and genomic clones derived from DLA DQ genes of Irish setter dogs. This breed was of interest, since it shows a high prevalence of gluten sensitive enteropathy (GSE), which may be a useful animal model for celiac disease (CD) of man. Interestingly, few of the alleles fou nd in Irish setters were identical to those previously detected in oth er breeds. Three novel DLA DQA and four novel DLA DQB alleles were dis covered in 19 unrelated dogs. Strong association between certain HLA D Q alleles and CD of man prompted us to screen the DQ alleles of member s of a family of gluten-sensitive Irish setter dogs. No haplotypes or alleles were shared by all affected dogs, but one frequent haplotype i n this family was also detected in an unrelated gluten-sensitive Irish setter; this haplotype was absent in the healthy dogs. This observati on warrants further investigation by screening the DQ alleles of a lar ge population of unrelated gluten-sensitive Irish setters.