Breed-specific variations in the coding region of toll-like receptor 4 in the domestic cat

Specific point mutations in the human toll-like receptor 4 (TLR4) confer altered risk for diverse diseases including sepsis, aspergillosis and inflammatory bowel disease. Some of these TLR4 polymorphisms are racially specific. We hypothesised that feline TLR4 polymorphisms might underlie an observed increased risk to infectious and inflammatory diseases in some cat breeds. The aim of this study was to identify breed-specific variations in the coding region of feline TLR4 and to model the effect of mutations on protein structure and function in silico. The entire coding region of TLR4 was sequenced in 8 groups (7 pure-bred, 1 crossbred) of domestic cats (Felis catus) comprising 158 individuals. Twenty-two single nucleotide polymorphisms (SNPs) were identified in TLR4, with 16 located in the coding region (11 non-synonymous) and four in the 3′UTR. Comparison of breed specific allelic frequencies indicated that Burmese and British shorthairs most commonly differed from other breeds. In silico analyses to predict the impact of the 11 non-synonymous variants indicated a deleterious effect on protein structure for one SNP (c.869 G > A), which was not associated with a specific breed. Overall, findings from this study do not support a role of TLR4 dysfunction in breed-predispositions to infectious diseases in domestic cats in Australia.