Association Analysis Between Sequence Variation Of Toll-like And RIG-I-like Receptor Genes And Disease Resistance Differences Among Yunnan Local Cattle Breeds

Yunnan local cattle breeds have been subjected to different strengths of natural selection and artificial selection and developed a number of merit traits such as high disease resistance, due to the long-term impact of complex and diverse natural environments and multi-ethnic socioeconomics and cultures. Yunnan local cattle breeds are composed of two main types-taurine cattle and zebu cattle. Besides marked morphological differences, there exist differences in disease resistance to multiple animal diseases between taurine and zebu cattle. For instance, taurine cattle show higher resistance to trypanosomosis than zebu cattle, whereas zebu cattle show higher resistance to theileriosis and tick infection than taurine cattle do. However, little is so far known about molecular mechanisms underlying disease resistance differences between taurine and zebu cattle. Therefore, we chose TOLL-like receptors (TLRs) and RIG-I-like receptors (RLRs) as representatives of pattern recognition receptors (PRRs) to investigate association between sequence variation of TLR (TLR3 and TLR8) and RLR (DDX58) genes and disease resistance differences among Yunnan local cattle breeds.In this study we analyzed a total of 144 samples from five Yunnan local cattle breeds, including 32 Zhaotong cattle,30 Dengchuan cattle,30 Wenshan cattle,20 Dianzhong cattle and 32 Yunnan humped cattle, among which Yunnan humped cattle are zebu type and other four cattle breeds are taurine type. First, the sequences of TLR3, TLR8 and DDX58 genes were determined in the five local cattle breeds; Second, we applied population genetic approaches to conduct genetics diversity analysis, construct median-joining networks, detect selection signatures and perform functional prediction of vairiable sites; Finally, we conducted association analysis between those key sequence variable sites and disease resistance differences among Yunnan local cattle breeds. The results revealed that:lower level of genetic diversity was found in Yunnan humped cattle, while higer levels of genetic diversity were found in other four breeds; The median-joining networks and haplotype analyses demonstated that the DDX58 gene showed greater genetic differentiation than the TLR3 and TLR8 genes did; Among three tested genes, signatures of balancing selection were only detected in TLR8 gene in Dengchuan cattle, Wenshan cattle and Zhaotong cattle; Functional prediction indicated that amino acid substitutions from taurine to zebu cattle were benign. In addition, it was found that there existed significant differences (P< 0.05, chi-square test) in distribution frequencies of those key sequence variable sites between zebu and taurine cattle. The obtained results suggest that there exist possible association between sequence variation of the three PPR genes and disease resistance differences among Yunan local cattle breeds, in particular, between zebu and taurine cattle. This study provides important genetic insights for conservation of zebu cattle resources and development of new cattle breed with high disease resistance.