Evidence for extensive DLA polymorphism in different dog populations

Abstract

Many of the genes within the Canine Major Histocompatibility Complex are highly polymorphic. Most of the alleles defined to date for DLA-DRB1, DQA1 and DQB1 come from the analysis of European or North American pure bred dogs. Little is known about DLA gene polymorphisms in other dog populations. We have studied Alaskan Husky dogs and Brazilian mongrel dogs and compared them with a panel of 568 European dogs and 40 Alaskan gray wolves. DNA sequence based typing was used to characterize a series of 12 Alaskan Huskies and 115 Brazilian mongrels for their DLA-DRB1, DQA1 and DQB1 alleles. Within these dogs, 22 previously undescribed DLA class II alleles were identified: 10 DRB1, 5 DQA1 and 7 DQB1 alleles. All these alleles were found in more than one animal, and, in some cases, as a homozygote. Several alleles initially observed in Alaskan gray wolves were found in these dogs. Each new allele was found in specific haplotypic combinations. Many new DLA class II haplotypes were identified. Several of the new alleles and haplotypes were also identified in the European dogs used for comparison. One new haplotype, containing a previously unknown DLA-DRB1 allele together with DQA1 and DQB1 alleles only seen before in gray wolves, was found in 20 Brazilian dogs, including three homozygous animals. It appears likely that the extent of polymorphism of the DLA genes will increase substantially as dogs from a wider geographic distribution are studied. This has major implications for the study of disease susceptibility and immune responsiveness in dogs.

Mechanism of Deletion Removing All Dystrophin Exons in a Canine Model for DMD Implicates Concerted Evolution of X Chromosome Pseudogenes

“…These features of the GSHPMD model favor its use in the rigorous study of cytotoxic immune responses to recombinant dystrophin expressed following regional or systemic gene therapy. Interestingly, intra-breed allelic diversity, while limited, has been identified within DLA-88, a dog leukocyte antigen (DLA) gene that displays the highest polymorphism of the MHC class I loci 42, 43, 44. Therefore, immunological studies within a single dog breed, such as the GSHPMD model, may result in varied responses based on DLA class I haplotype, a result that can be expected in clinical trials due to the highly polymorphic HLAs encoding MHC I 45 .…”

Dog Leukocyte Antigen Class II–Associated Genetic Risk Testing for Immune Disorders of Dogs: Simplified Approaches Using Pug Dog Necrotizing Meningoencephalitis as a Model

“…Kennedy, personal communication, 2010). 17,18,21 Although the potential for allelic variation within the DLA class II region is great, this potential is limited by natural linkage disequilibrium in the DLA and by more recent inbreeding. Thus, DLA class II diversity among A linked STR marker test also worked well for determining DLA class II-associated risk for NME in Pugs.…”

“…Homozygous and heterozygous (mixed) sequences were resolved, and allele nomenclature was assigned according to an international standard. 18 All DLA-DRB1, -DQA1, and -DQB1 alleles identified among Pugs 10 were previously known from this and other breeds.…”

Inferring the ancestry of African wild dogs that returned to the Serengeti-Mara

“…Sequence-based typing was conducted according to the methods outlined in Marsden et al (2009) and Kennedy et al (2002). In brief, we amplified exon 2 of the MHC class II DLA-DRB1 locus (hereafter referred to as DRB) by PCR.…”