Breed-specific variations in the coding region of the feline TLR4
Point mutations in toll-like receptor 4 (TLR4) in humans have been associated with increased risk of infectious diseases, eg. tuberculosis and aspergillosis, and non-infectious diseases, eg. gastric carcinoma and atherosclerosis. In some instances, variations in disease susceptibility associated with TLR4 mutations have been shown to be racially specific. The aim of this study was to evaluate the coding region of feline TLR4 to identify breed-specific variations in sequence and the possible effect of these on protein structure and function. Exonic and flanking DNA of TLR4 was sequenced from 158 individual cats of 9 breeds and compared to the previously reported cDNA sequence. Twenty-two single nucleotide polymorphisms (SNPs) were identified. Sixteen polymorphisms (11 non-synonymous) were located in the coding region and four polymorphisms were located in the URT 3’ of TLR4. The effect of the non-synonymous SNPs on protein structure was predicted and revealed that a single SNP and resulting amino acid substitution, R289Q, had a significant effect on protein structure. Breed allelic frequencies were compared for 118 unrelated cats for the identified SNPs. Allelic frequencies differed between at least two breeds for 8 of the SNPs (2 synonymous, 2 non-synonymous, 4 in the flanking regions). Within these, Burmese and BSHs most commonly differed from the other breeds. These findings do not support a role of TLR4 dysfunction in breed-predisposition to infection in domestic cats in Australia.