Abstract
BackgroundThe exact aetiology of canine sino-nasal aspergillosis (SNA) is unknown. In man, dysfunction in innate immunity, particularly in the function of pattern recognition receptors, is implicated in the pathogenesis of inflammatory sino-nasal disease and in fungal diseases. Associations between single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and these diseases have been identified. Similarly, in dogs SNPs in genes encoding TLRs may be important in the pathogenesis of SNA. The aims of the present study were (1) to identify the presence of non-synonymous SNPs in the coding regions of the TLR2, 4 and 9 genes in dogs suffering from SNA, and (2) to investigate the SNP genotypes in dogs with SNA compared with a control population.ResultsDirect sequencing of nine dogs of various breeds with SNA revealed two non-synonymous SNPs in the coding region of TLR2, eight in TLR4 and four in TLR9. These non-synonymous SNPs were further evaluated in a case-control study of affected Golden Retrievers, Labrador Retrievers, Rottweilers and Beaucerons. Genotyping was performed using a combination of allele-specific primers and hydrolysis probe assays in 31 dogs with SNA and 31controls. No significant difference in minor allele frequency was identified between these groups, for all studied SNPs, in any of the four breeds.ConclusionsThese findings do not support a role for non-synonymous SNPs in the TLR 2, 4 and 9 coding regions in the pathogenesis of canine SNA, but do not exclude a role for innate immunity in the pathogenesis of the disease.
Highlights
The exact aetiology of canine sino-nasal aspergillosis (SNA) is unknown
Selection of single nucleotide polymorphisms The initial part of the study focused on a mutational analysis of TLR2, 4 and 9 genes in nine dogs with SNA belonging to various breeds
single nucleotide polymorphisms (SNPs) genotyping and association study To assess the significance of the identified SNPs, the allelic frequencies in a group of dogs with SNA belonging to four breeds commonly affected by SNA (Golden Retriever, Labrador Retriever, Rottweiler and Beauceron Sheepdog) were compared with those found in control dogs of the same breeds (Table 2), and no significant difference was found
Summary
Dysfunction in innate immunity, in the function of pattern recognition receptors, is implicated in the pathogenesis of inflammatory sino-nasal disease and in fungal diseases. Associations between single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and these diseases have been identified. Toll-like receptors (TLRs) are situated on these cells and on dendritic cell populations in this location and appear to play crucial roles in the distinction between commensal flora and PAMPs. Single nucleotide polymorphisms (SNPs) within the TLR genes have been reported to impact the immune reaction to microbial antigens, and to be associated with the incidence and outcome of infections [3]. Sino-nasal aspergillosis (SNA) is a cause of chronic rhinitis, and the disease is most often caused by A. fumigatus [11]. As the disease usually affects systemically healthy dogs, and A. fumigatus is a ubiquitous fungus, a local immune deficiency in affected dogs has been suggested [13]
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