Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs
| Autor: | Thierry Olivry, Robert Goggs, Theresa O'Toole, Lorna J. Kennedy, Robert B. Rose, Natasha J. Olby, Greg Buhrman, Lhoucine Chdid, Steven G. Friedenberg, Julien Guillaumin, Kathryn M. Meurs |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Hemolytic anemia Models Molecular Candidate gene Genotype Protein Conformation animal diseases Immunology chemical and pharmacologic phenomena Disease Polymorphism Single Nucleotide Article Autoimmune Diseases 03 medical and health sciences Structure-Activity Relationship Dogs Gene Frequency Meta-Analysis as Topic Research Support N.I.H. Extramural Genetics medicine Journal Article Animals Genetic Predisposition to Disease Dog Diseases Allele Allele frequency Alleles Binding Sites biology Dog leukocyte antigen Research Support Non-U.S. Gov't Histocompatibility Antigens Class I Reproducibility of Results Atopic dermatitis Exons biochemical phenomena metabolism and nutrition medicine.disease 030104 developmental biology Phenotype Amino Acid Substitution Immune System Diseases biology.protein bacteria Peptides |
| Zdroj: | 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, vol. 68, no. 3, pp. 205-17 . https://doi.org/10.1007/s00251-015-0894-6 |
| DOI: | 10.1007/s00251-015-0894-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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