Haplotype Disequilibrium in the <i>TLR</i> Genes of Czech Red Pied Cattle

Hybrid resequencing of the antibacterial innate immune genes coding for toll-like receptors, namely <i>TLR1</i>, <i>TLR2</i>, <i>TLR4</i>, <i>TLR5</i>, and <i>TLR6</i>, using HiSeq and PacBio technologies of pooled population samples of Czech Simmental (Czech Red) cattle allowed us to determine haplotypes formed by the polymorphisms present. Directly determined haplotypes within the range of the large proximal amplicon in <i>TLR2</i> formed two clusters in the network tree graph. The distribution of the statistically reconstructed haplotypes based on individual genotyping of the present SNPs was consistent. Similarly, the statistically reconstructed haplotypes in <i>TLR5</i> and <i>TLR6</i> formed two clusters. The trend of bimodal distribution was also observed in <i>TLR4</i>, while the limited diversity of <i>TLR1</i> did not allow for any conclusion. The observed bimodal distribution is consistent with earlier reports for cattle populations worldwide. The stability of this phenomenon cannot be ascribed to historical origin but rather to a long-term effect of balancing selection. The equilibrium might be based on two different essential functions performed by the <i>TLR</i> genes or their products. The formation of two kinds of heterodimers by the <i>TLR2</i> product, namely, <i>TLR2</i>/<i>TLR1</i> and <i>TLR2</i>/<i>TLR6</i> with different ligand specificities, is considered to be a particular case. On the other hand, the better expression of the bimodal groups in the 5′-proximal SNPs supports the localization of the selection targets in the upstream regulatory regions or the functional interactions in the proximal part of the transcripts.