Evolution of the bovine TLR gene family and member associations with Mycobacterium avium subspecies paratuberculosis infection.

摘要: Members of the Toll-like receptor (TLR) gene family occupy key roles in mammalian innate immune system by functioning as sentries for detection invading pathogens, thereafter provoking host responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) one putative nonsense SNP. Bayesian haplotype reconstructions median joining networks revealed sharing between Bos taurus indicus breeds at every locus, specialized beef dairy could not be differentiated despite an average polymorphism density 1 marker/158 bp. Collectively, 160 tagSNPs two tag insertion-deletion mutations (indels) were sufficient predict 100% variation variable sites both subspecies their hybrids, whereas 118 tagIndel predictively captured 235 B. t. taurus. Polyphen SIFT analyses amino acid (AA) replacements encoded SNPs indicated that up 32% AA substitutions expected impact protein function. Classical newly developed tests diversity provide strong support balancing selection operating on TLR3 TLR8, purifying acting TLR10. An investigation persistence continuity linkage disequilibrium (r2≥0.50) adjacent also supported presence TLR8. A case-control study employing validated from genes recognizing bacterial ligands six potentially eliciting small effects susceptibility Mycobacterium avium spp paratuberculosis infection cattle. The results this will broadly domestic cattle research providing necessary foundation explore several avenues translational genomics, potential marker-assisted vaccination.