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

Çınar, Mehmet Ulaş; Hızlısoy, Harun; Akyüz, Bilal; Arslan, Korhan; Aksel, Esma Gamze; Gümüşsoy, Kadir Semih

doi:10.1007/s12041-018-1008-7

Cited by 14 publications

(8 citation statements)

References 47 publications

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“…Thus, additional approaches, PLOS ONE such as genomic selection for cattle less susceptible to pTB to control pTB, are needed. Similar to our results, variability among cattle breeds in their susceptibility to pTB were identified in different experiments and support that selection for enhanced resistance to the disease is possible [21,[25][26][27]. Association of bovine pTB susceptibility with EDN2 was first identified with a GWAS [18] and SNP-based gene-set enrichment analysis for MAP infection detected via tissue infection or fecal shedding by using in 245 US Holsteins [19].…”

Section: Discussionsupporting

confidence: 87%

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The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population

et al. 2020

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Paratuberculosis (pTB), also known as Johne's disease (JD), is a contagious, chronic, and granulomatous inflammatory disease of the intestines of ruminants which is caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection, resulting in billions of dollars in economic losses worldwide. Since, currently, no effective cure is available for MAP infection, it is important to explore the genetic variants that affect the host MAP susceptibility. The aim of this study was to analyze a potential association between EDN2 synonymous gene mutations (rs110287192, rs109651404 and rs136707411), that modifies susceptibility to pTB. EDN2 rs110287192, rs109651404 and rs136707411 mutations were genotyped in 68 infected and 753 healthy animals from East Anatolian Red crossbred, Anatolian Black crossbred and Holstein breed cattle by using Custom TaqMan SNP Genotyping Assays. For pTB status, serum antibody levels S/P � 1.0 were assessed in carriers of the different EDN2 genotypes. EDN2 rs110287192 mutation showed a significant association with bovine pTB (adj. p < 0.05). For rs110287192 locus, the odd ratios for GG and TG genotypes versus TT genotypes were 1.73; (95% CI = 0.34-8.59) and 0.53 (95% CI = 0.12-2.37) respectively, which indicated that proportion of TG heterozygotes were significantly higher in control animals as compared to pTB animals. On the other hand, while rs136707411 mutation showed a suggestive association with pTB status in the examined cattle population (nominal p < 0.05); no association was detected between rs109651404 genotypes and pTB status. Selecting animals against rs110287192-GG genotype may decrease the risk of pTB in cattle of the Bos taurus taurus subspecies.

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Section: Discussionsupporting

confidence: 87%

“…Animals that were both clinically negative and serologically negative were considered healthy (controls). Further details regarding sample collection and ELISA diagnostic tests have been published elsewhere [21]. The study population was found to consist of 68 infected and 750 healthy animals.…”

Section: Sample Collectionmentioning

confidence: 99%

The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population

et al. 2020

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“…It is known that MAP uses tissue-resident macrophages as its primary reservoir for survival and multiplication (10)(11)(12). Interestingly, genetic variations in numerous candidate genes expressed in macrophages are associated with resistance/susceptibility to MAP infection, notably the NOD2 (13,14), IL10 (15)(16)(17)(18), SLC11A1, and Toll-like receptor genes (19,20).…”

Section: Introductionmentioning

confidence: 99%

Identification of Long Non-coding RNA Isolated From Naturally Infected Macrophages and Associated With Bovine Johne's Disease in Canadian Holstein Using a Combination of Neural Networks and Logistic Regression

et al. 2021

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Mycobacterium avium ssp. paratuberculosis (MAP) causes chronic enteritis in most ruminants. The pathogen MAP causes Johne's disease (JD), a chronic, incurable, wasting disease. Weight loss, diarrhea, and a gradual drop in milk production characterize the disease's clinical phase, culminating in death. Several studies have characterized long non-coding RNA (lncRNA) in bovine tissues, and a previous study characterizes (lncRNA) in macrophages infected with MAP in vitro. In this study, we aim to characterize the lncRNA in macrophages from cows naturally infected with MAP. From 15 herds, feces and blood samples were collected for each cow older than 24 months, twice yearly over 3–5 years. Paired samples were analyzed by fecal PCR and blood ELISA. We used RNA-seq data to study lncRNA in macrophages from 33 JD(+) and 33 JD(–) dairy cows. We performed RNA-seq analysis using the “new Tuxedo” suite. We characterized lncRNA using logistic regression and multilayered neural networks and used DESeq2 for differential expression analysis and Panther and Reactome classification systems for gene ontology (GO) analysis. The study identified 13,301 lncRNA, 605 of which were novel lncRNA. We found seven genes close to differentially expressed lncRNA, including CCDC174, ERI1, FZD1, TWSG1, ZBTB38, ZNF814, and ZSCAN4. None of the genes associated with susceptibility to JD have been cited in the literature. LncRNA target genes were significantly enriched for biological process GO terms involved in immunity and nucleic acid regulation. These include the MyD88 pathway (TLR5), GO:0043312 (neutrophil degranulation), GO:0002446 (neutrophil-mediated immunity), and GO:0042119 (neutrophil activation). These results identified lncRNA with potential roles in host immunity and potential candidate genes and pathways through which lncRNA might function in response to MAP infection.

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“…Among TLRs, TLR2 has a key role in recognizing the lipopeptide, peptidoglycan, mycolic acids, and lipoarabinomannan PAMPs of gram-positive bacteria and mycobacteria 12,13,14 . In the search for host alleles in uencing susceptibility to Johne's disease, candidate gene approaches targeting TLR gene family have revealed associations in cattle [15][16][17][18][19] and sheep 20 . Our interest in TLR2 was based on three observations: 1) its increased mRNA abundance soon after MAP infection in sheep 21 , 2) its actively involvement in the innate immune response against tuberculosis 22,23 and paratuberculosis diseases 15,16 , and 3) its missense variant association with susceptibility to mycobacterial infections in humans and farm animals 24 .…”

Section: Introductionmentioning

confidence: 99%

Association of TLR2 Haplotypes Encoding Q650 With Reduced Susceptibility to Ovine Johne’s Disease in Turkish Sheep

Yaman¹,

Aymaz

Keleş

et al. 2021

Preprint

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Ovine Johne’s disease (OJD) is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and carries a potential zoonotic risk for humans. Selective breeding strategies for reduced OJD susceptibility would be welcome tools in disease eradication efforts, if available. The Toll-like receptor 2 gene (TLR2) plays an important signaling role in immune response to MAP, and missense variants are associated with mycobacterial infections in mammals. Our aim was to identify and evaluate ovine TLR2 missense variants for association with OJD in Turkish sheep. Eleven TLR2 missense variants and 17 haplotype configurations were identified in genomic sequences of 221 sheep from 61 globally-distributed breeds. The five most frequent haplotypes were tested for OJD association in 102 matched pairs of infected and uninfected ewes identified in 2257 Turkish sheep. Ewes with one or two copies of TLR2 haplotypes encoding glutamine (Q) at position 650 (Q650) in the Tir domain were 6.6-fold more likely to be uninfected compared to ewes with arginine (R650) at that position (CI95 = 2.6 to 16.9, p-value = 3.7x10-6). The protective TLR2 Q650 allele was present in at least 25% of breeds tested and thus may facilitate selective breeding for sheep with reduced susceptibility to OJD.

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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

Cited by 14 publications

References 47 publications

The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population

The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population

Identification of Long Non-coding RNA Isolated From Naturally Infected Macrophages and Associated With Bovine Johne's Disease in Canadian Holstein Using a Combination of Neural Networks and Logistic Regression

Association of TLR2 Haplotypes Encoding Q650 With Reduced Susceptibility to Ovine Johne’s Disease in Turkish Sheep

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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

Cited by 14 publications

References 47 publications

The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population

The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population

Identification of Long Non-coding RNA Isolated From Naturally Infected Macrophages and Associated With Bovine Johne's Disease in Canadian Holstein Using a Combination of Neural Networks and Logistic Regression

Association of TLR2&nbsp;Haplotypes Encoding Q650 With Reduced Susceptibility to Ovine Johne’s Disease in Turkish Sheep

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Association of TLR2 Haplotypes Encoding Q650 With Reduced Susceptibility to Ovine Johne’s Disease in Turkish Sheep