Single Nucleotide Polymorphisms of Toll-Like Receptor 4 Gene in the Two Breeds Rabbit

doi:10.14088/j.cnki.issn0439-8114.2018.11.025

Abstract

Abstract: TLR4 could detect endotoxin by identifying lipopolysaccharide （LPS） and play a key role in host defense mediated by Gram-negative bacteria（LPS）,therefore, TLR4 is a significant candidate gene for rabbit diseases resistance research. To identify nucleotide polymorphisms between two different breeds we designed primer pairs that amplified fragments of coding sequence（CDS） of 12 individuals, and compared the sequences. Comparative sequence analysis indicated that 3 SNPs were identified, all were non-synonymous SNPs. Two nonsynonymous SNPs（G628T and A653C） were located in the LRR domains of the predicted protein. The nonsynonymous SNPs in the LRR domains, especially related to leucine residues, may dramatically alter the ability to identified extracellular pathogens. The identification of these polymorphisms reported here increases the resource of genetic markers useful for association analyses with disease resistance and provides an important theoretical basis for disease resistant breeding of meat rabbits.

Key words: meat rabbits, TLR4 gene, SNP, nonsynonymous SNPs, disease resistance

CLC Number:

S829.1

ZHANG Xiang-yu, LI Jin-liang, LI Xu-ting, LI Si-chong, ZHANG Min, WANG Wu-yan, YANG Rui. Single Nucleotide Polymorphisms of Toll-Like Receptor 4 Gene in the Two Breeds Rabbit[J]. HUBEI AGRICULTURAL SCIENCES, 2018, 57(11): 100-102.

References

[1] MEDZHITOV R,PRESTON-HURBURT P,JANEWAY C A.A human homologue of the Drosophila Toll protein signals activation of adaptor immunity[J]. Nature,1997,388:394-400.
[2] ROCK F L,HARDIUM G,TIMANS J C,et al.A family of human receptors structurally related to Drosophila Toll[J].Proc Natl Acad Sci USA,1998,95(2):588-593.
[3] TAKEDA K,AKIRA S.Toll-like receptors in innate immunity[J]. Int Immunol,2005,17(1):1-14.
[4] UENISHI H,SHINKAI H.Porcine Toll-like receptors:The front line of pathogen monitoring and possible implications for disease resistance[J]. Dev Comp Immunol,2009,33(3):353-361.
[5] SHARMA B S,LEYVA I,SCHENKEL F,et al.Association of toll like receptor 4 polymorphisms with somatic cell score and lactation persistency in Holstein bulls[J]. J Dairy Sci,2006, 89(9):3626-3635.
[6] WERLING D,HOPE J C,HOWARD C J,et al.Differential production of cytokines,reactive oxygen and nitrogen by bovine macrophages and dendritic cells stimulated with toll-like receptor agonists[J]. Immunology,2004,111:41-52.
[7] JANEWAY JR C A,MEDZHITOV R. Innate immune recognition[J]. Annu Rev Immunol,2002,20:197-216.
[8] BOCHUD P Y,HERSBERGER M,TAFFÉ P,et al.Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection[J]. AIDS,2007,21:441-446.
[9] SHINKAI H,TANAKA M,MOROZUMI T,et al.Biased distribution of single nucleotide polymorphisms(SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes[J]. Immunogenetics,2006,58:324-330.
[10] CARRINGTON M,NELSON G W,MARTIN M P,et al.HLA and HIV-1:Heterozygote advantage and B*35-Cw*04 disadvantage[J]. Science,1999,283:1748-1752.
[11] FUJITA M,INTO T,YASUDA M,et al.Involvement of leucine residues at positions 107,112, and 115 in a leucine-rich repeat motif of human Toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans[J]. J Immunol,2003,171:3675-3683.
[12] SMIRNOVA I,HAMBLIN M T,MCBRIDE C,et al.Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans[J]. Genetics,2001,158:1657-1664.
[13] POLTORAK A,HE X L,SMIRNOVA I.Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice:Mutations in TLr4 gene[J].Science,1998,282:2085-2088.
[14] PUTHOTHU B,FORSTER J,HEINZMANN A,et al.TLR4 and CD14 polymorphisms in respiratory syncytial virus associated disease[J]. Dis Markers,2006,22(5-6):303-308.
[15] ACHYUT B R.Association of Toll-like receptor-4(Asp299Gly and Thr399Ileu)gene polymorphisms with gastritis and precancerous lesions[J]. Human Immunology,2007,10(6):1-7.
[16] BJORKBACKA H,KUNJATHOOR V V,MOORE K J,et al.Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling path ways[J].Nat Med,2004,10:416-421.
[17] GIBOT S,CARIOU A,DROUET L,et al.Association between a genomic polymorphism within the CD14 locus and septic shock susceptibility and mortality rate[J].Crit Care Med,2002, 30:969-973.
[18] MICHELSEN K S,WONG M H,SHAH P K,et al.Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient inapolipoprotein E[J].Proc Natl Acad Sci USA,2004, 101:10679-10684.
[19] LORENZ E,MIRA J P,FREES K L,et al.Relevance of mutations in the TLR4 receptor in patients with gram-negative septic shock[J]. Arch Intern Med,2002,162(9):1028-1032.
[20] ARBOUR N C,LORENZ E,SCHUTTE B C,et al.TLR4 mutations are associated with endotoxin hyporesponsiveness in humans[J]. Nat Genet,2000,25(2):187-191.