Computational characterization of deleterious SNPs in Toll-like receptor gene that potentially cause mastitis in dairy cattle

Abstract

Mastitis is a highly prevalent disease in dairy cattle that cause high economic losses, because of the diminished production of milk and decreased milk quality. Toll-like receptors (TLRs) play a crucial role in the induction of innate immune responses and especially, in the mammary gland cells, it can pick out the invading pathogens. Gene expression shows considerable variation occurs in TLRs and several SNP's are linked with altered susceptibility to infectious diseases. Through this study, the deleterious SNPs in TLR2, TLR4, TLR6 and TLR10 are identified and reported along with available inhibitors interactions with native and mutant form of TLR. Initially, the experimentally reported non-synonymous SNPs of different types of TLRs is retrieved and analyzed by SFIT, PolyPhen, I- Mutant, Consurf and HOPE servers. The results obtained from various tools used in the study shows that the deleterious non-synonymous SNPs (nsSNPs) of TLR2 may responsible for the mutation of Arginine to Histidine at 563 and Threonine to Methionine at 605 and exhibit greatest impact on protein stability. Additionally, the 3D structure of both native and mutant forms of TLR2 is modeled and the interactions are analyzed with currently available inhibitors. Overall, the present study reveals the deleterious nsSNPs in TLR2 with mutation (T563H and T605M), which may affect the structure and function of TLR2.