Autoimmune diseases are caused by a breakdown in the tolerance that evades immune responses to self-antigens, and it is assumed that genetic and environmental factors collectively contribute to their development. To date, numerous disease susceptibility gene loci have been identified using comprehensive genome analysis methods such as genome-wide association studies (GWAS). Among these, genes encoding co-stimulatory molecules that play an important role in antigen presentation from Human Leukocyte Antigen (HLA) to T cell antigen receptor (TCR) have relatively many disease susceptibility gene loci common to multiple autoimmune diseases. It has been revealed that CD80, ICOSLG, CD40, CD58, CD28, CTLA4, and PDCD1, are involved in autoimmune diseases because of specific genetic variants by the post-GWAS analyses using in silico analyses and the genome editing technologies such as CRISPR/Cas9.

The domestic dog (Canis lupus familiaris) is one of the main target animals for small animal clinical medicine. Consolidation of the polymorphism information of Dog MHC (Dog leukocyte antigen: DLA) genes is necessary for discovering disease-associations and developing advanced veterinary medicine of dogs such as regenerative medicine by allo-transplantation of somatic or hematopoietic stem cells and cancer immunotherapy. We have so far conducted polymorphism analysis of the DLA genes in 829 dogs of 59 breeds collected in Japan. In this review, we outlined the current information of the DLA polymorphisms including our research findings such as haplotype structures of the DLA class I loci, estimation of the DLA haplotypes composed of the DLA class I and class II loci, and characteristics of intra- and inter-breed DLA diversity.