Single-nucleotide polymorphisms in CLEC7A, CD209 and TLR4 gene and their association with susceptibility to paratuberculosis in Indian cattle
The aim of this study was to identify the single-nucleotide polymorphisms (SNPs) in bovine candidate genes CLEC7A, CD209 and TLR4, and explore the association between these SNPs with the occurrence of bovine paratuberculosis (PTB) disease. For this purpose, 549 animals were screened by a panel of four diagnostic tests, namely Johnin PPD test, ELISA test, faecal microscopy and IS900 blood PCR against Mycobacterium avium ssp. paratuberculosis (MAP) to develop case–control populations. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Genotypic–phenotypic associations were assessed by the PROC-LOGISTIC procedure of SAS 9.3. Of the seven SNPs; rs110353594 in CLEC7A gene and rs8193046 in TLR4 gene were found to be associated with PTB. For SNP rs110353594, odds of CC and CT genotypes vs TT genotype was 1.543 (0.420–5.667; 95% CI) and 0.284 (0.104–0.774; 95% CI), respectively which means that CT genotype was more resistant than TT and CC genotypes against bovine PTB. For SNP rs8193046, odds of AA and AG genotypes versus GG genotype was 0.947 (0.296–3.034; 95% CI) and 3.947 (1.555–10.022; 95% CI), respectively, i.e. probability for getting an infection in animals with AG genotype was 3.94 times more as compared to GG genotype. Hence, a selection programme favouring CT genotype for rs110353594 and against AG genotype for rs8193046 may be beneficial for conferring resistance against bovine PTB.
Keywordsimmune response paratuberculosis resistance single-nucleotide polymorphism TLR4 gene.
We thank Director, ICAR-Indian Veterinary Research Institute, Izatnagar, India for providing necessary facilities and funding of this work with grant no. IXX09774.
- Buza J. J., Mori Y., Bari A. M., Aodon-geril H. H., Hirayama S., Shu Y. et al. 2003 Mycobacterium avium subsp. paratuberculosis infection causes suppression of RANTES, monocyte chemoattractant protein 1, and tumor necrosis factor alpha expression in peripheral blood of experimentally infected cattle. Infect. Immun. 71, 7223–7227.PubMedPubMedCentralCrossRefGoogle Scholar
- Cinar M. U., Hizlisoy H., Akyüz B., Arslan K., Aksel E. G. and Gümüşsoy K. S. 2018 Polymorphisms in toll-like receptor (TLR) 1, 4, 9 and SLC11A1 genes and their association with paratuberculosis susceptibility in Holstein and indigenous crossbred cattle in Turkey. J. Genet. 97, 1147–1154.CrossRefGoogle Scholar
- Correa-Valencia N. M., Ramírez N. F., Olivera M. and Fernández-Silva J. A. 2016 Milk yield and lactation stage are associated with positive results to ELISA for Mycobacterium avium subsp. paratuberculosis in dairy cows from Northern Antioquia, Colombia: a preliminary study. Trop. Anim. Health Prod. 48, 1191–1200.PubMedCrossRefGoogle Scholar
- Coussens P. M., Verman N., Coussens M. A., Elftman M. D. and McNulty A. M. 2004 Cytokine gene expression in peripheral blood mononuclear cells and tissues of cattle infected with Mycobacterium avium subsp. paratuberculosis: evidence for an inherent proinflammatory gene expression pattern. Infect. Immun. 72, 1409–1422.PubMedPubMedCentralCrossRefGoogle Scholar
- Jensen K., Makins G. D., Kaliszewska A., Hulme M. J., Paxton E. and Glass E. J. 2009 The protozoan parasite Theileria annulata alters the differentiation state of the infected macrophage and suppresses musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors. Int. J. Parasitol. 39, 1099–1108.PubMedPubMedCentralCrossRefGoogle Scholar
- Koets A., Santema W., Mertens H., Oostenrijk D., Keestra M., Overdijk M. et al. 2010 Susceptibility to paratuberculosis infection in cattle is associated with single nucleotide polymorphisms in toll-like receptor 2 which modulate immune responses against Mycobacterium avium subspecies paratuberculosis. Prev. Vet. Med. 93, 305–315.PubMedCrossRefGoogle Scholar
- Kumar S. 2015 Single nucleotide polymorphism in candidate genes and their association with occurrence of paratuberculosis in cattle. M.V.Sc. Thesis. IVRI (Deemed University), Bareilly, UP, India.Google Scholar
- Kumar N., Ganguly I., Singh R., Deb S. M., Kumar S., Sharma A. et al. 2011 DNA polymorphism in the SLC11A1 gene and its association with brucellosis resistance in Indian zebu (Bos indicus) and crossbred (Bos indicus× Bos taurus) Cattle. Asian-Australas. J. Anim. Sci. 24, 898–904.CrossRefGoogle Scholar
- Kumar S., Kumar S., Singh R., Chauhan A., Agrawal S., Kumar A. et al. 2017 Investigation of genetic association of single nucleotide polymorphisms in SP110 Gene with occurrence of paratuberculosis disease in Cattle. Int. J. Livest. Res. 7, 81–88.Google Scholar
- Sadana T., Singh R. V., Singh S. V., Saxena V. K., Sharma D., Singh P. K. et al. 2015 Single nucleotide polymorphism of SLC11A 1, CARD15, IFNG and TLR2 genes and their association with Mycobacterium avium subspecies paratuberculosis infection in native Indian cattle population. Indian J. Biotechnol. 14, 469–475.Google Scholar
- Sambrook J. and Russel D. W. 2001 Molecular cloning- A laboratory manual. 3rd edition. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.Google Scholar
- Singh S. V., Singh A. V., Singh R., Sharma S., Shukla N., Misra S. et al. 2000 Sero-Prevalence of Johne’s disease in buffaloes and cattle population of North India using indigenous ELISA kit based on native Mycobacterium avium subspecies paratuberculosis ‘Bison Type’ Genotype of Goat Origin, Comp. Immunol. Microbiol. Infect. Dis. 31, 419–433.CrossRefGoogle Scholar
- Singh S. V., Singh P. K., Gupta S., Chaubey K. K., Singh B., Kumar A. et al. 2013a Comparison of microscopy and blood-PCR for the diagnosis of clinical Johne’s disease in domestic ruminants. Iran J. Vet. Res. 14, 345–349.Google Scholar
- Singh S. V., Singh A. V., Singh P. K., Gupta S., Singh H., Singh B. et al. 2013c Evaluation of ‘Indigenous Vaccine’ developed using ‘Indian Bison Type’Genotype of Mycobacterium avium subspecies paratuberculosis Strain ‘S5’of goat origin in a sheep flock endemic for johne’s disease: a three years trial in India. World J. Vaccines. 3, 52–59.CrossRefGoogle Scholar
- Slana I., Paolicchi F., Janstova B., Navratilova P. and Pavlik I. 2008 Detection methods for Mycobacterium avium subsp paratuberculosis in milk and milk products: a review. Vet. Med. (Praha). 53, 283.Google Scholar
- Vazquez P., Ruíz-Larrañaga O., Garrido J. M., Iriondo M., Manzano C., Agirre M. et al. 2014 Genetic association analysis of paratuberculosis forms in Holstein-Friesian Cattle, HindawiPublishing Corporation. Vet. Med. Int. 2014, Article ID 321327.Google Scholar
- Yadav R., Sharma A. K., Singh R., Sonwane A., Kumar A., Chauhan A. et al. 2014 An association study of SNPs with susceptibility to bovine paratuberculosis infection in cattle. Indian J. Anim. Sci. 84, 490–493.Google Scholar