Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection

Fisher, Colleen A.; Bhattarai, Eric K.; Osterstock, Jason B.; Dowd, Scot E.; Seabury, Paul M.; Vikram, Meenu; Whitlock, Robert H.; Schukken, Ynte H.; Schnabel, Robert D.; Taylor, Jeremy F.; Womack, James E.; Seabury, Christopher M.

Haplotype association tests were performed in PHASE 2.1 [31] . Briefly, for dairy cattle with disease classifications based on bacterial culture status of MAP, we tested the hypothesis that haplotypes differ among cases and controls for all genes evaluated in the single marker association analysis (68 cases, 270 controls, n = 338 total). For maximum LD-based resolution of haplotypes, we used all variable markers within seven bovine TLR genes that recognize bacterial ligands. Significance was estimated via 1,000 permutations. Figure S1 Median joining (MJ) haplotype networks constructed for bovine TLR1, TLR2, TLR4, TLR5, TLR6, TLR7 , and TLR9 using haplotypes predicted for all cattle. For all loci except TLR7, all cattle is defined as follows: n = 96 AI sires, 31 breeds; 48 Purebred Angus; 405 Holstein cattle. For TLR7, only the sequencing discovery panel was genotyped and is represented (n = 96 AI sires, 31 breeds). Because MJ networks require the absence of recombination [66] , each network represents intragenic regions of elevated LD. Haplotypes predicted for B. t. taurus, B. t. indicus and hybrids (termed ''composites'') are color coded. Numbers indicate SNP and indel positions in numerical order (see Table S2 for SNP information). Node sizes are proportional to haplotype frequency, and all branch lengths are drawn to scale. Alphabetized letters at nodes represent the breed distribution of each haplotype (Table S4 ). Median vectors are indicated as ''mv''. (PPTX)