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Canine Genet Epidemiol. 2019 Feb 15;6:2. doi: 10.1186/s40575-019-0070-7. eCollection 2019.

DLA class II risk haplotypes for autoimmune diseases in the bearded collie offer insight to autoimmunity signatures across dog breeds.

Author information

1
1Department of Animal Science, University of California, One Shields Ave, Davis, CA 95616 USA.
2
2Brazilian National Council for Scientific and Technological Development (CNPq) fellow, Brasília, Brazil.
3
3Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
4
4Research Programs Unit, Molecular Neurology, and Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
5
5Folkhälsan Institute of Genetics, Helsinki, Finland.

Abstract

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.

KEYWORDS:

(3–10): Dog; Addison’s disease; Autoimmune; DLA; MHC; SLO

Conflict of interest statement

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed were in accordance with the ethical standards of the University of California, Davis (IACUC #20402) and University of Helsinki, Finland (permit ESAVI/6054/04.10.03/ 2012). All UK samples consisted of residual blood remaining after diagnostic testing and were collected in accordance with guidelines of the Royal College of Veterinary Surgeons, UK and the Veterinary Surgeons Act 1966. For this reason ethical committee approval was not required. All samples were collected with informed and written owner consent.Not applicable.Lorna Kennedy is Managing Editor on Canine Genetics and Epidemiology. The other authors declare no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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