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1.  Assessment of Toll-like receptor 2, 4 and 9 SNP genotypes in canine sino-nasal aspergillosis 
BMC Veterinary Research  2014;10:187.
The 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.
Direct 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.
These 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.
PMCID: PMC4143572  PMID: 25266752
Sino-nasal aspergillosis; Dog; Toll-like receptor gene; Single nucleotide polymorphism
2.  CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs 
Nature genetics  2010;43(1):72-78.
Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry1. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.
PMCID: PMC3509786  PMID: 21131972
3.  Efficacy of intrasinusal administration of bifonazole cream alone or in combination with enilconazole irrigation in canine sino-nasal aspergillosis: 17 cases 
The Canadian Veterinary Journal  2010;51(2):164-168.
This study evaluated the effect of 1% bifonazole cream in the treatment of canine sino-nasal aspergillosis (SNA). The cream was instilled through perendoscopically placed catheters into the frontal sinuses and was used either as single therapy after debridement (DC) or as adjunctive therapy after 2% enilconazole infusion (DEC). Twelve dogs were treated initially with DEC: 7 and 3 of these dogs were free of disease after 1 and 2 procedures, respectively, while 2 dogs were cured after DC was used as a second procedure. Five dogs were treated with DC only: in 3 dogs with moderate disease, cure was obtained after a single procedure while, in 2 debilitated patients, cure could not be confirmed. Topical administration of 1% bifonazole cream appears as an effective therapy in SNA, either as an adjunctive therapy to enilconazole infusion or as sole therapy in moderately affected patients.
PMCID: PMC2808281  PMID: 20436862

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