Polymorphisms within the Toll-like receptor (TLR)-2, -4, and -6 genes in cattle

Abstract

Toll-like receptors (TLR) have an important role in the defence against a variety of infectious diseases. TLR recognize various microbial components and are important in the innate immune response to pathogens and in crosstalk between innate immunity and adaptive immunity. Polymorphisms in TLRs influence their abilities of recognition of pathogen-derived molecules and therefore could be of great relevance in livestock selection once genetic variation in these loci has been associated with resistance. Several single nucleotide polymorphisms (SNPs) within TLR genes have been described in humans and some of them seem to be associated with susceptibility to infection diseases. Recently, all the 10 TLR genes have been mapped in cattle by radiation hybrid panel.

In this study, we screened the nucleotide sequences of bovine TLR2, TLR4, and TLR6 genes (located on BTA17, BTA8 and BTA6, respectively) searching for SNPs potentially linked with disease resistance. We could identify 11 SNPs that were used for screening 900 individuals belonging to 16 different bovine European breeds. Eight of the analysed breeds resulted polymorphic at all the analysed loci, and six of the loci were polymorphic in all the breeds. Allelic frequencies, Gene Diversity, Heterozygosity and PIC were calculated. Heterozygosity and PIC ranged respectively from 0.05 to 0.47 and from 0.06 and 0.37. Heterozygosity and F_st were calculated using the Fdist software (http://www.rubic.rdg.ac.uk/~mab/software.html). Population phylogeny datasets were built by bootstrapping 200,000 replications on real data using a coalescent model. None of the SNPs were found to lie outside the 95% confidence limits assumed for conditional joint distribution of F_st vs mean heterozygosity, and therefore the genes do not appear to be under selection in the analysed samples according to the employed model. However, several SNPs were not in HW equilibrium. We hypothesize that some of the polymorphisms were fixated since many generations within breed and the coalescent model could not be powerful enough to reveal selection event so far in the past.