Single Nucleotide Polymorphisms in TLR4 Gene and Endometritis Resistance in River Buffalo (Bubalus bubalis)

摘要

Toll-like receptor (TLR) genes play a crucial role in pathogen recognition and subsequent activation of the innate immune response. The role of TLR4in the initiation of inflammatory and immune response makes it a suitable candidate gene for marker-assisted selection to enhance disease resistance in dairy animals. The present study was undertaken to characterize the distribution of single nucleotide polymorphisms (SNPs) in TLR4 coding region, and to test their role as potential risk factor for the occurrence of endometritis in river buffalo Egyptian breed (Bubalus bubalis). The analysis of the entire coding sequences (CDs) enabled the identification of 13 non-synonymous SNP. A statistical correlation was observed between resistance to endometritis and the genotype CC at the 2464 C A locus and AA genotype at the 2465 A C. Moreover, a correlation was seen between susceptibility to endometritis and the heterozygous and recessive homozygous genotypes of these SNPs. Haplotype reconstruction of the TLR4 gene revealed a statistical significance of haplotype frequencies between healthy and diseased cases by performing a permutation test which retrieved significant association with the occurrence of the disease in the coding region of TLR4.PolyPhen 2 analysis revealed two amino acid substitutions which may have a potential structural and functional significance. The current study describes some novel SNPs in TLR4 gene of river buffalo Egyptian breed and their association with the endometritis disease, therefore suggesting a possible positional marker in the buffalo genome that may be related to such a disease.