Single Nucleotide Polymorphisms in 5’ Upstream Region of Bovine TLR4 Gene Affecting Expression Profile and Transcription Factor Binding Sites

Abstract

The present study in the 5' upstream region of TLR4 gene revealed four Single Nucleotide Polymorphisms (SNPs) in Vrindavani and Tharparkar cattle. The polymorphic information content (PIC), heterozygosity and allelic diversity values were low to moderate for these SNPs. In Vrindavani cattle, one SNP was found to be in Hardy-Weinberg Equilibrium (HWE) and the remaining three were found to be in linkage disequilibrium (LD) as indicated statistically (P > 0.05). In Tharparkar cattle, two SNPs were found to be in HWE and were not in LD as indicated statistically (P > 0.05). These SNPs were used for construction of haplotypes. In-silico analysis of these SNPs predicted abolition of eight transcription factor binding sites and creation of eight new sites. The quantitative real time PCR analysis did not show any significant variation of gene expression among haplotypes. However, gene expression between breed was found to be significant (P < 0.05) which suggested that upstream region of bovine TLR4 gene has a crucial role in its expression. These findings in TLR4 gene offer essential evidence that can be useful in future research exploring its role in immunity. TLR4 can be used as a marker for selection for disease resistance in bovines.

Association of toll-like receptor 4 (TLR 4) gene exon 3 variants with serostatus of the ovine Johne’s disease (paratuberculosis) in Turkish sheep

“…Recent studies have revealed that the TLR gene family could play a crucial role in innate immunity. It was reported that the variations at 5′ upstream of the bovine TLR4 gene altered the expression profile and could affect immune response [25]. Additionally, it has been demonstrated that expression of the TLR gene family in the course of OJD significantly differed when compared to healthy sheep [26].…”

Understanding eco-immunology of bacterial zoonoses and alternative therapeutics toward "One Health"

“…TLR-4 is an important candidate gene for imparting disease resistance in livestock as it is involved in pathogen recognition in most of Gram-negative bacterial infections that lead to the initiation of the inflammatory and immune responses. There is a single report where the unfavorable alleles at P-226 (putative promoter region) and E3+1656 (Exon 3) of TLR-4 SNPs if removed, can result in disease-resistant bovines [47]. Identification of non-synonymous SNPs and novel variants of TLR2, TLR4, and TLR6 genes were recently established which helped in identifying disease-resistant breeds of European cattle.…”

Candidate Gene Polymorphism vis-a-vis Immune Response to Important Infectious Diseases in Bovines

“…reported differential expression profile of innate immune response genes including TLR2, NFKB1, TNF, IFNG, IL2, CXCR3, PRKCB1, RPS6KB2, STK17B and EEF1. Mishra et al, (2018) identified single nucleotide polymorphisms in 5' upstream region of bovine TLR4 gene affecting expression profile and transcription factor binding sites. These findings in TLR4 gene offer essential evidence that can be useful in future research exploring its role in immunity and TLR4 can be used as a marker for selection for disease resistance in bovines.…”