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 journalArticle

7 Scopus citations

Abstract

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 (US)
Pages (from-to)205-217
Number of pages13
JournalImmunogenetics
Volume68
Issue number3
DOIs
StatePublished - Mar 1 2016

Keywords

  • Canine
  • Dog leukocyte antigen
  • Immune-mediated disease
  • Major histocompatibility complex class Ib

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    Friedenberg, S. G., Buhrman, G., Chdid, L., Olby, N. J., Olivry, T., Guillaumin, J., O’Toole, T., Goggs, R., Kennedy, L. J., Rose, R. B., & Meurs, K. M. (2016). Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs. Immunogenetics, 68(3), 205-217. https://doi.org/10.1007/s00251-015-0894-6