Haplotype variation in bovine Toll-like receptor 4 and computational prediction of a positively selected ligand-binding domain

• DOI: 10.1073/pnas.1333957100
• Publication Date: 2003-09-02T17:27:00Z
• Authors: Stephen N. White; Kristen H. Taylor; Colette A. Abbey; Clare A. Gill; James E. Womack
• Keywords: Nonsynonymous substitution; Coding region; SNP

Toll-like receptor 4 (TLR4) is a cell-surface that activates innate and adaptive immune responses. Because it recognizes broad class of pathogen-associated molecular patterns presented by lipopolysaccharides lipoteichoic acid, TLR4 candidate gene for resistance to large number diseases. In particular, mouse models suggest as major agents in bovine respiratory disease Johne's disease. The coding sequence divided into three exons, with intron/exon boundaries intron sizes similar those human transcript variant 1. We amplified each exon 40 individuals from 11 breeds screened the single-nucleotide polymorphisms (SNPs). identified 32 SNPs, 28 which are sequence, an average one SNP per 90 bp sequence. Eight SNPs were nonsynonymous potentially alter specificity pathogen recognition or efficiency signaling. To evaluate functional importance these we used codon-substitution detect diversifying selection extracellular region may physically interact ligands. One located within this region, other substitutions adjacent regions coreceptor molecules. found 20 haplotypes can be assigned geographic ranges origin. Haplotype-tagging analysis indicated 12 need genotyped distinguish haplotypes. These data provide basic understanding variation supply haplotype markers association studies.