Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs

Steven G Friedenberg, Greg Buhrman, Lhoucine Chdid, Natasha J Olby, Thierry Olivry, Julien Guillaumin, Theresa O'Toole, Robert Goggs, Lorna J Kennedy, Robert B Rose, Kathryn M Meurs

Research output: Contribution to journalArticlepeer-review


Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.

Original languageEnglish
Pages (from-to)205-17
Number of pages13
Issue number3
Publication statusPublished - Mar 2016


  • Alleles
  • Amino Acid Substitution
  • Animals
  • Autoimmune Diseases
  • Binding Sites
  • Dog Diseases
  • Dogs
  • Exons
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Histocompatibility Antigens Class I
  • Immune System Diseases
  • Meta-Analysis as Topic
  • Models, Molecular
  • Peptides
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Protein Conformation
  • Reproducibility of Results
  • Structure-Activity Relationship
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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