title: Non-synonymous genetic variation in exonic regions of canine Toll-like receptors.
abstract: BACKGROUND
  Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) considered to be the primary sensors of pathogens in innate immunity. Genetic variants could be associated to differences in breed innate immune response to pathogens and thus to susceptibility to infections or autoimmune diseases. There is therefore great interest in the characterization of canine TLRs.
  
  
  RESULTS
  Polymorphisms in canine TLRs have been characterized by massive sequencing after enrichment of their exonic regions. DNAs from 335 dogs (seven different breeds) and 100 wolves (two different populations) were used in pools. The ratio of SNP discovery was 76.5% (in relation to CanFam 3.1); 155 out of 204 variants identified were new. Functional annotation identified 64 non-synonymous variants (43 new), 73 synonymous variants (56 new) and 67 modifier variants (57 new). 12 out of 64 non-synonymous variants are breed or wolf specific. TLR5 has been found to be the most polymorphic among canine TLRs. Finally, a TaqMan OpenArray® plate containing 64 SNPs with a possible functional effect in the protein (4 frameshifts and 60 non-synonymous codons) has been designed and validated.
  
  
  CONCLUSIONS
  Non-synonymous genetic variation has been characterized in exonic regions of canine Toll-like Receptors. The TaqMan OpenArray® plate developed to capture the individual variability that affects protein function will allow high-throughput genotyping either to study association to infection susceptibility or even TLR evolution in the canine genome.
authors.affiliation: Molecular Genetics Veterinary Service. Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Spain ; Vetgenomics. Ed Eureka. Parc de Recerca UAB, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cuscó
authors.affiliation: Molecular Genetics Veterinary Service. Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Armand
authors.initials: A
authors.lastname: Sánchez
authors.affiliation: Vetgenomics. Ed Eureka. Parc de Recerca UAB, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Altet
authors.affiliation: Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA USA.
authors.forename: Lluís
authors.initials: L
authors.lastname: Ferrer
authors.affiliation: Molecular Genetics Veterinary Service. Veterinary School, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Francino
keywords: Canine; Dog; Innate immunity; Non-synonymous SNPs; Polymorphism; SNPs; TLRs; Toll-like receptor