DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds
| Autor: | Hannes Lohi, Marjo K. Hytönen, Lorna J. Kennedy, Thomas R. Famula, Anita M. Oberbauer, Andrea D. Short, Janelle M. Belanger, Liza C. Gershony, Myly Le |
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| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
lcsh:QH426-470 endocrine system diseases 040301 veterinary sciences Addison’s disease Population biology.animal_breed Context (language use) Dog [(3–10)] SLO Major histocompatibility complex Autoimmune Disease (3–10): Dog 0403 veterinary science 03 medical and health sciences 0302 clinical medicine lcsh:Zoology medicine Genetics 2.1 Biological and endogenous factors lcsh:QL1-991 Allele Aetiology education Autoimmune disease education.field_of_study Bearded collie biology Dog leukocyte antigen Inflammatory and immune system Research Haplotype 04 agricultural and veterinary sciences General Medicine medicine.disease lcsh:Genetics DLA biology.protein Addison's disease MHC 030215 immunology Autoimmune |
| Zdroj: | Canine genetics and epidemiology, vol 6, iss 1 Canine Genetics and Epidemiology Canine Genetics and Epidemiology, Vol 6, Iss 1, Pp 1-13 (2019) |
| Popis: | Background Primary hypoadrenocorticism (Addison’s disease, AD) and symmetrical lupoid onychodystrophy (SLO) are two clinical conditions with an autoimmune etiology that occur in multiple dog breeds. In man, autoimmunity is associated with polymorphisms in immune-related genes that result in a reduced threshold for, or defective regulation of, T cell activation. The major histocompatibility complex (MHC) class II genes encode molecules that participate in these functions, and polymorphisms within these genes have been associated with autoimmune conditions in dogs and humans. Bearded collies have a relatively high prevalence of autoimmune diseases, particularly AD and SLO. Our study assessed the relationship between particular MHC (dog leukocyte antigen, DLA) class II haplotypes and the two autoimmune diseases most common in this breed. Moreover, five unrelated breeds at increased risk for AD were studied for comparative purposes and analyzed in the context of extant literature. Results A single DLA class II three-locus haplotype, determined by sequence-based typing, was associated with increased risk for AD (DLA-DRB1*009:01/DQA1*001:01/DQB1*008:02) in bearded collies. Comparative analysis with the five additional breeds showed limited allele sharing, with DQA1*001:01 and DQB1*002:01 being the only alleles observed in all breeds. A distinct three-locus risk haplotype (DLA-DRB1*001:01/DQA1*001:01/DQB1*002:01) was associated with AD in the West Highland white terrier and Leonberger. Two different risk haplotypes were associated with increased risk for SLO in the bearded collie (DLA-DRB1*018:01/DQA1*001:01/DQB1*002:01 and DLA-DRB1*018:01/DQA1*001:01/ DQB1*008:02). Conclusion Two-locus DQ haplotypes composed of DLA-DQA1*001:01 in association with DLA-DQB1*002:01 or DLA-DQB1*008:02 make up the four risk haplotypes identified in the present study and are also found in other risk haplotypes previously associated with diabetes mellitus and hypothyroidism across different dog breeds. Our findings build upon previously published data to suggest that this two-locus (DQ) model serves as a good indicator for susceptibility to multiple organ-specific autoimmune diseases in the canine population. However, it is also clear that additional loci are necessary for actual disease expression. Investigation of affected and unaffected dogs carrying these predisposing DQ haplotype signatures may allow for the identification of those additional genetic components that determine autoimmune disease expression and organ specificity. Electronic supplementary material The online version of this article (10.1186/s40575-019-0070-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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