{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:28:50Z","timestamp":1785364130289,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T00:00:00Z","timestamp":1728604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"name":"National Key Research and Development Program of China","award":["2022YFD1302201"],"award-info":[{"award-number":["2022YFD1302201"]}]},{"name":"National Key Research and Development Program of China","award":["32072806"],"award-info":[{"award-number":["32072806"]}]},{"name":"National Key Research and Development Program of China","award":["32372970"],"award-info":[{"award-number":["32372970"]}]},{"name":"National Key Research and Development Program of China","award":["2024NYGG005-6"],"award-info":[{"award-number":["2024NYGG005-6"]}]},{"name":"National Key Research and Development Program of China","award":["20221086"],"award-info":[{"award-number":["20221086"]}]},{"name":"National Key Research and Development Program of China","award":["20230978"],"award-info":[{"award-number":["20230978"]}]},{"name":"National Key Research and Development Program of China","award":["2022JBGS0025"],"award-info":[{"award-number":["2022JBGS0025"]}]},{"name":"National Key Research and Development Program of China","award":["22JY075"],"award-info":[{"award-number":["22JY075"]}]},{"name":"National Key Research and Development Program of China","award":["2022HX144"],"award-info":[{"award-number":["2022HX144"]}]},{"name":"National Key Research and Development Program of China","award":["H2023060246"],"award-info":[{"award-number":["H2023060246"]}]},{"name":"National Natural Science Foundation of China","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"name":"National Natural Science Foundation of China","award":["2022YFD1302201"],"award-info":[{"award-number":["2022YFD1302201"]}]},{"name":"National Natural Science Foundation of China","award":["32072806"],"award-info":[{"award-number":["32072806"]}]},{"name":"National Natural Science Foundation of China","award":["32372970"],"award-info":[{"award-number":["32372970"]}]},{"name":"National Natural Science Foundation of China","award":["2024NYGG005-6"],"award-info":[{"award-number":["2024NYGG005-6"]}]},{"name":"National Natural Science Foundation of China","award":["20221086"],"award-info":[{"award-number":["20221086"]}]},{"name":"National Natural Science Foundation of China","award":["20230978"],"award-info":[{"award-number":["20230978"]}]},{"name":"National Natural Science Foundation of China","award":["2022JBGS0025"],"award-info":[{"award-number":["2022JBGS0025"]}]},{"name":"National Natural Science Foundation of China","award":["22JY075"],"award-info":[{"award-number":["22JY075"]}]},{"name":"National Natural Science Foundation of China","award":["2022HX144"],"award-info":[{"award-number":["2022HX144"]}]},{"name":"National Natural Science Foundation of China","award":["H2023060246"],"award-info":[{"award-number":["H2023060246"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["2022YFD1302201"],"award-info":[{"award-number":["2022YFD1302201"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["32072806"],"award-info":[{"award-number":["32072806"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["32372970"],"award-info":[{"award-number":["32372970"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["2024NYGG005-6"],"award-info":[{"award-number":["2024NYGG005-6"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["20221086"],"award-info":[{"award-number":["20221086"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["20230978"],"award-info":[{"award-number":["20230978"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["2022JBGS0025"],"award-info":[{"award-number":["2022JBGS0025"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["22JY075"],"award-info":[{"award-number":["22JY075"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["2022HX144"],"award-info":[{"award-number":["2022HX144"]}]},{"name":"Key Technologies Demonstration of Animal Husbandry in the Shaanxi province","award":["H2023060246"],"award-info":[{"award-number":["H2023060246"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["2022YFD1302201"],"award-info":[{"award-number":["2022YFD1302201"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["32072806"],"award-info":[{"award-number":["32072806"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["32372970"],"award-info":[{"award-number":["32372970"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["2024NYGG005-6"],"award-info":[{"award-number":["2024NYGG005-6"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["20221086"],"award-info":[{"award-number":["20221086"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["20230978"],"award-info":[{"award-number":["20230978"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["2022JBGS0025"],"award-info":[{"award-number":["2022JBGS0025"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["22JY075"],"award-info":[{"award-number":["22JY075"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["2022HX144"],"award-info":[{"award-number":["2022HX144"]}]},{"name":"Inner Mongolia Autonomous Region Open Competition Projects","award":["H2023060246"],"award-info":[{"award-number":["H2023060246"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["2022YFD1302201"],"award-info":[{"award-number":["2022YFD1302201"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["32072806"],"award-info":[{"award-number":["32072806"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["32372970"],"award-info":[{"award-number":["32372970"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["2024NYGG005-6"],"award-info":[{"award-number":["2024NYGG005-6"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["20221086"],"award-info":[{"award-number":["20221086"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["20230978"],"award-info":[{"award-number":["20230978"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["2022JBGS0025"],"award-info":[{"award-number":["2022JBGS0025"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["22JY075"],"award-info":[{"award-number":["22JY075"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["2022HX144"],"award-info":[{"award-number":["2022HX144"]}]},{"name":"Major Project of the Shaanxi Provincial Department of Education","award":["H2023060246"],"award-info":[{"award-number":["H2023060246"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["2022YFD1302201"],"award-info":[{"award-number":["2022YFD1302201"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["32072806"],"award-info":[{"award-number":["32072806"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["32372970"],"award-info":[{"award-number":["32372970"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["2024NYGG005-6"],"award-info":[{"award-number":["2024NYGG005-6"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["20221086"],"award-info":[{"award-number":["20221086"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["20230978"],"award-info":[{"award-number":["20230978"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["2022JBGS0025"],"award-info":[{"award-number":["2022JBGS0025"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["22JY075"],"award-info":[{"award-number":["22JY075"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["2022HX144"],"award-info":[{"award-number":["2022HX144"]}]},{"name":"Horizontal Project of Northwest Agriculture and Forestry University","award":["H2023060246"],"award-info":[{"award-number":["H2023060246"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["2022YFD1302201"],"award-info":[{"award-number":["2022YFD1302201"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["32072806"],"award-info":[{"award-number":["32072806"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["32372970"],"award-info":[{"award-number":["32372970"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["2024NYGG005-6"],"award-info":[{"award-number":["2024NYGG005-6"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["20221086"],"award-info":[{"award-number":["20221086"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["20230978"],"award-info":[{"award-number":["20230978"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["2022JBGS0025"],"award-info":[{"award-number":["2022JBGS0025"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["22JY075"],"award-info":[{"award-number":["22JY075"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["2022HX144"],"award-info":[{"award-number":["2022HX144"]}]},{"name":"Xinjiang Uygur Autonomous Region Scientific Research and Innovation Platform Construction Project \u201cState Key Laboratory of Genetic Improvement and Germplasm Innovation of Grass-fed Livestock Co-construction by the Province and Ministry\u201d","award":["H2023060246"],"award-info":[{"award-number":["H2023060246"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The cytotoxic T lymphocyte-associated antigen-4 (CTLA4) gene, a member of the immunoglobulin superfamily, is crucial for maintaining immune homeostasis and preventing autoimmune diseases. Studies have shown that polymorphisms in the CTLA4 gene are linked to an increased risk of brucellosis in humans, but its association with brucellosis in goats remains unexplored. In this study, the tissue expression profile of CTLA4 in goats was investigated, and the correlation between InDel polymorphisms in the CTLA4 gene and susceptibility to brucellosis in goats was examined. The findings reveal the widespread expression of CTLA4 in goat tissues, particularly in the spleen and testes. The tested goat populations presented genotypes insertion\/insertion (II), insertion\/deletion (ID), and deletion\/deletion (DD) at both the P1 and P2 loci, and an association analysis revealed significant differences in the distribution of genotypes and allele frequencies at the P1 and P2 loci of the CTLA4 gene between the Brucella goat case and the control groups (p &lt; 0.05). Specifically, compared with the II genotype, the P1 and P2 loci were significantly associated with an elevated risk of brucellosis development in goats under both the codominant (ID\/II) and dominant (ID + DD\/II) models (P1, p = 0.042, p = 0.016; P2, p = 0.011, p = 0.014). Additionally, haplotype analysis indicated that haplotypes IP1DP2, DP1IP2, and DP1DP2 were significantly associated with an increased risk of brucellosis in goats compared to the reference haplotype IP1IP2 (p = 0.029, p = 0.012, p = 0.034). Importantly, the Lipopolysaccharide (LPS) stimulation of peripheral blood monocytes and\/or macrophages from goats with the II, ID, and DD genotypes resulted in increased CTLA4 expression levels in the II genotype, leading to a robust LPS-induced inflammatory response. Through bioinformatic analysis, the observed effect of the InDel locus on Brucella pathogenesis risk in goats could be attributed to the differential binding of the transcription factors nuclear factor kappaB (NF-\u03baB) and CCAAT\/enhancer-binding protein \u03b1 (C\/EBP\u03b1). These findings offer potential insights for breeding strategies against brucellosis.<\/jats:p>","DOI":"10.3390\/ijms252010948","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T08:10:16Z","timestamp":1728634216000},"page":"10948","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Goat Cytotoxic T Lymphocyte-Associated Antigen-4 Gene: mRNA Expression and Association Analysis of Insertion\/Deletion Variants with the Risk of Brucellosis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2232-2101","authenticated-orcid":false,"given":"Congliang","family":"Wang","sequence":"first","affiliation":[{"name":"Shaanxi Centre of Stem Cells Engineering & Technology, College of Veterinary Medicine, Northwest Agriculture & Forestry University, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaofei","family":"Ren","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of Livestock Biology, Northwest Agriculture & Forestry University, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Shaanxi Centre of Stem Cells Engineering & Technology, College of Veterinary Medicine, Northwest Agriculture & Forestry University, Xianyang 712100, China"},{"name":"Key Laboratory of Livestock Biology, Northwest Agriculture & Forestry University, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyue","family":"Song","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Animal Science, Xinjiang Academy of Animal Husbandry Sciences, Urumqi 830000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Qu","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats, Life Science Research Center, Yulin University, Yulin 719000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9788-8592","authenticated-orcid":false,"given":"Jinlian","family":"Hua","sequence":"additional","affiliation":[{"name":"Shaanxi Centre of Stem Cells Engineering & Technology, College of Veterinary Medicine, Northwest Agriculture & Forestry University, Xianyang 712100, China"},{"name":"Key Laboratory of Livestock Biology, Northwest Agriculture & Forestry University, Xianyang 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122986","DOI":"10.1016\/j.lfs.2024.122986","article-title":"The development of a human Brucella mucosal vaccine: What should be considered?","volume":"355","author":"Tian","year":"2024","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, Y., Tan, D., Xue, S., Shen, C., Ning, H., Cai, C., and Liu, Z. (2021). Prevalence, distribution and risk factors for brucellosis infection in goat farms in Ningxiang, China. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-021-02743-x"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Siengsanan-Lamont, J., Kong, L., Heng, T., Khoeun, S., Tum, S., Selleck, P.W., Gleeson, L.J., and Blacksell, S.D. (2023). Risk mapping using serologic surveillance for selected One Health and transboundary diseases in Cambodian goats. PLoS Neglected Trop. Dis., 17.","DOI":"10.1371\/journal.pntd.0011244"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Rossetti, C.A., Arenas-Gamboa, A.M., and Maurizio, E. (2017). Caprine brucellosis, A historically neglected disease with significant impact on public health. PLoS Neglected Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005692"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/j.1469-0691.2005.01204.x","article-title":"Correlation between animal and human brucellosis in Italy during the period 1997\u20132002","volume":"11","author":"Petrini","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e1231","DOI":"10.1111\/tbed.14495","article-title":"Brucellosis in Ethiopia: A comprehensive review of literature from the year 2000\u20132020 and the way forward","volume":"69","author":"Sibhat","year":"2022","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.chom.2017.07.017","article-title":"A Brucella Type IV Effector Targets the COG Tethering Complex to Remodel Host Secretory Traffic and Promote Intracellular Replication","volume":"22","author":"Miller","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.theriogenology.2019.08.007","article-title":"Goat SPEF2, Expression profile, indel variants identification and association analysis with litter size","volume":"139","author":"Chen","year":"2019","journal-title":"Theriogenology"},{"key":"ref_9","first-page":"742","article-title":"An overview of Brucellosis","volume":"20","author":"Haque","year":"2011","journal-title":"Mymensingh Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ran, X., Chen, X., Wang, M., Cheng, J., Ni, H., Zhang, X.X., and Wen, X. (2018). Brucellosis seroprevalence in ovine and caprine flocks in China during 2000\u20132018: A systematic review and meta-analysis. BMC Vet. Res., 14.","DOI":"10.1186\/s12917-018-1715-6"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.actatropica.2018.10.002","article-title":"Brucellosis seroprevalence in dairy cattle in China during 2008\u20132018: A systematic review and meta-analysis","volume":"189","author":"Ran","year":"2019","journal-title":"Acta Trop."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1017\/S146625231600013X","article-title":"Prevalence of tuberculosis, brucellosis and trypanosomiasis in cattle in Tanzania: A systematic review and meta-analysis","volume":"17","author":"Alonso","year":"2016","journal-title":"Anim. Health Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Njeru, J., Wareth, G., Melzer, F., Henning, K., Pletz, M.W., Heller, R., and Neubauer, H. (2016). Systematic review of brucellosis in Kenya: Disease frequency in humans and animals and risk factors for human infection. BMC Public Health, 16.","DOI":"10.1186\/s12889-016-3532-9"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Dahl, M.O. (2020). Brucellosis in food-producing animals in Mosul, Iraq: A systematic review and meta-analysis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235862"},{"key":"ref_15","first-page":"57","article-title":"The economic impact attributable to brucellosis among goat farms in Peninsula Malaysia and cost benefit analysis","volume":"5","author":"Bamaiyi","year":"2015","journal-title":"Res. Opin. Anim. Vet. Sci."},{"key":"ref_16","first-page":"191","article-title":"Economic losses due to Brucella melitensis infection in sheep and goats","volume":"6","author":"Sulima","year":"2010","journal-title":"Tamilnadu J. Vet. Anim. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.cimid.2012.09.001","article-title":"A \u201cOne Health\u201d surveillance and control of brucellosis in developing countries, moving away from improvisation","volume":"36","author":"Godfroid","year":"2013","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.mbs.2012.11.012","article-title":"Modeling the transmission dynamics of sheep brucellosis in Inner Mongolia Autonomous Region, China","volume":"242","author":"Hou","year":"2013","journal-title":"Math. Biosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cvfa.2010.10.003","article-title":"Control and eradication of Brucella melitensis infection in sheep and goats","volume":"27","author":"Blasco","year":"2011","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1139\/cjm-2017-0179","article-title":"Brucella melitensis M5-90\u0394bp26 as a potential live vaccine that allows for the distinction between natural infection and immunization","volume":"63","author":"Li","year":"2017","journal-title":"Can. J. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.micinf.2017.12.006","article-title":"Alternative strategies for vaccination to brucellosis","volume":"20","author":"Pascual","year":"2018","journal-title":"Microbes Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.theriogenology.2022.09.001","article-title":"Goat SMAD family member 1 (SMAD1): mRNA expression, genetic variants, and their associations with litter size","volume":"193","author":"Wijayanti","year":"2022","journal-title":"Theriogenology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1183\/09031936.00141808","article-title":"CTLA4 gene polymorphisms are associated with chronic bronchitis","volume":"34","author":"Zhu","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41577-022-00693-5","article-title":"The link between circulating follicular helper T cells and autoimmunity","volume":"22","author":"Walker","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ghorbaninezhad, F., Masoumi, J., Bakhshivand, M., Baghbanzadeh, A., Mokhtarzadeh, A., Kazemi, T., Aghebati-Maleki, L., Shotorbani, S.S., Jafarlou, M., and Brunetti, O. (2022). CTLA-4 silencing in dendritic cells loaded with colorectal cancer cell lysate improves autologous T cell responses in vitro. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.931316"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1111\/1756-185X.14219","article-title":"CTLA-4 polymorphisms in Thai patients with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis","volume":"24","author":"Louthrenoo","year":"2021","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.micinf.2010.10.015","article-title":"Cell-mediated immunity in human brucellosis","volume":"13","author":"Skendros","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sun, H.L., Du, X.F., Tang, Y.X., Li, G.Q., Yang, S.Y., Wang, L.H., Li, X.W., Ma, C.J., and Jiang, R.M. (2021). Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06730-3"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/1348-0421.12119","article-title":"Investigation of CTLA-4 and CD86 gene polymorphisms in Iranian patients with brucellosis infection","volume":"58","author":"Moghadampour","year":"2014","journal-title":"Microbiol. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cui, Y., Yan, H., Wang, K., Xu, H., Zhang, X., Zhu, H., Liu, J., Qu, L., Lan, X., and Pan, C. (2018). Insertion\/Deletion Within the KDM6A Gene Is Significantly Associated With Litter Size in Goat. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00091"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1615\/CritRevImmunol.v26.i5.30","article-title":"Host immune responses to the intracellular bacteria Brucella, does the bacteria instruct the host to facilitate chronic infection?","volume":"26","author":"Baldwin","year":"2011","journal-title":"Crit. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nri1349","article-title":"Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity","volume":"4","author":"Chen","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5784","DOI":"10.4049\/jimmunol.162.10.5784","article-title":"Lymphoproliferative disorder in CTLA-4 knockout mice is characterized by CD28-regulated activation of Th2 responses","volume":"162","author":"Khattri","year":"1999","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1084\/jem.20082492","article-title":"Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies","volume":"206","author":"Peggs","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"106909","DOI":"10.1016\/j.micpath.2024.106909","article-title":"Design a novel of Brucellosis preventive vaccine based on IgV_CTLA-4 and multiple epitopes via immunoinformatics approach","volume":"195","author":"He","year":"2024","journal-title":"Microb. Pathog."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8368","DOI":"10.3390\/cimb46080493","article-title":"Association of CTLA-4 (AT)n Variants in Basal Cell Carcinoma and Squamous Cell Carcinoma Patients from Western Mexico","volume":"46","author":"Valle","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_37","first-page":"e50091","article-title":"The Variant Allele Frequency of CTLA-4 rs11571317 (\u2212658 C\/T) Polymorphism With Colorectal Cancer Susceptibility in the Saudi Population and Other Ethnic Groups","volume":"15","author":"Akhtar","year":"2023","journal-title":"Cureus"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Ghoneim, M.E., Sheashaa, H., Wafa, E., Awadalla, A., Ahmed, A.E., Sobh, M., and Shokeir, A.A. (2024). Impact of CD 28, CD86, CTLA-4 and PD-1 genes polymorphisms on acute renal allograft rejection and graft survival among Egyptian recipients. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-52195-0"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1016\/j.ygeno.2020.06.050","article-title":"Association of TNF rs668920841 and INRA111 polymorphisms with caprine brucellosis: A case-control study of candidate genes involved in innate immunity","volume":"112","author":"Hasenauer","year":"2020","journal-title":"Genomics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1007\/s11250-019-02154-z","article-title":"Association of single nucleotide polymorphism in NLRC3, NLRC5, HIP1, and LRP8 genes with fecal egg counts in goats naturally infected with Haemonchus contortus","volume":"52","author":"Omar","year":"2020","journal-title":"Trop. Anim. Health Prod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e2309455121","DOI":"10.1073\/pnas.2309455121","article-title":"Demography and environment modulate the effects of genetic diversity on extinction risk in a butterfly metapopulation","volume":"121","author":"DiLeo","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0169-5347(02)02489-8","article-title":"Inbreeding effects in wild populations","volume":"17","author":"Keller","year":"2002","journal-title":"Trends Ecol. Evol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Qu\u00e9m\u00e9r\u00e9, E., Rossi, S., Petit, E., Marchand, P., Merlet, J., Game, Y., Galan, M., and Gilot-Fromont, E. (2020). Genetic epidemiology of the Alpine ibex reservoir of persistent and virulent brucellosis outbreak. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-61299-2"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.vetmic.2007.10.033","article-title":"Association of microsatellite (GT)n polymorphism at 3\u2032UTR of NRAMP1 with the macrophage function following challenge with Brucella LPS in buffalo (Bubalus bubalis)","volume":"129","author":"Ganguly","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tvjl.2010.09.028","article-title":"Chromosomal localisation and genetic variation of the SLC11A1 gene in goats (Capra hircus)","volume":"190","author":"Vacca","year":"2011","journal-title":"Vet. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1128\/IAI.00948-06","article-title":"Protective effect of the Nramp1 BB genotype against Brucella abortus in the water buffalo (Bubalus bubalis)","volume":"75","author":"Capparelli","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lou, L., Bao, W., Liu, X., Song, H., Wang, Y., Zhang, K., Gao, W., Li, H., Tu, Z., and Wang, S. (2018). An Autoimmune Disease-Associated Risk Variant in the TNFAIP3 Gene Plays a Protective Role in Brucellosis That Is Mediated by the NF-\u03baB Signaling Pathway. J. Clin. Microbiol., 56.","DOI":"10.1128\/JCM.01363-17"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.4049\/jimmunol.172.8.4893","article-title":"CTLA-4 blockage increases resistance to infection with the intracellular protozoan Trypanosoma cruzi","volume":"172","author":"Martins","year":"2004","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, P.H., Wu, M.F., Hsu, C.Y., Lin, S.Y., Chang, Y.N., Lee, H.S., Wei, Y.F., and Shu, C.C. (2021). The Dynamic Change of Immune Checkpoints and CD14+ Monocytes in Latent Tuberculosis Infection. Biomedicines, 9.","DOI":"10.3390\/biomedicines9101479"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1007\/s11033-012-2245-0","article-title":"Analysis on DNA sequence of TSHB gene and its association with reproductive seasonality in goats","volume":"40","author":"Huang","year":"2013","journal-title":"Mol. Biol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.immuni.2014.02.006","article-title":"Noncanonical NF-\u03baB pathway controls the production of type I interferons in antiviral innate immunity","volume":"40","author":"Jin","year":"2014","journal-title":"Immunity"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1084\/jem.20150218","article-title":"Nuclear factor \u03baB-inducing kinase activation as a mechanism of pancreatic \u03b2 cell failure in obesity","volume":"212","author":"Malle","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Oeckinghaus, A., and Ghosh, S. (2009). The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol., 1.","DOI":"10.1101\/cshperspect.a000034"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cellsig.2015.11.005","article-title":"Toll-like receptor-3 mediates HIV-1 transactivation via NF\u03baB and JNK pathways and histone acetylation, but prolonged activation suppresses Tat and HIV-1 replication","volume":"28","author":"Bhargavan","year":"2016","journal-title":"Cell Signal."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Qu, H., Zong, Q., Wang, H., Wu, S., Cai, D., and Bao, W. (2022). C\/EBP\u03b1 Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.881289"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Mart\u00ednez, E.G., and Rodr\u00edguez-Mart\u00ednez, J.A. (2024). Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases. Front. Biosci. (Sch. Ed.), 16.","DOI":"10.31083\/j.fbs1601004"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"346","DOI":"10.3382\/ps.2011-01758","article-title":"Differences in the early response of hatchlings of different chicken breeding lines to Salmonella enterica serovar Enteritidis infection","volume":"91","author":"Schokker","year":"2012","journal-title":"Poult. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Kim, Y.C., Won, S.Y., and Jeong, B.H. (2019). Absence of single nucleotide polymorphisms (SNPs) in the open reading frame (ORF) of the prion protein gene (PRNP) in a large sampling of various chicken breeds. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6315-8"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"558","DOI":"10.14202\/vetworld.2019.558-564","article-title":"Prevalence of Caprine brucellosis in Anhui province, China","volume":"12","author":"Rahman","year":"2019","journal-title":"Vet. World"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1093\/nar\/25.22.4692","article-title":"Universal and rapid salt-extraction of high quality genomic DNA for PCR-based techniques","volume":"25","author":"Aljanabi","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.14202\/vetworld.2015.1183-1188","article-title":"Genotyping of major histocompatibility complex Class II DRB gene in Rohilkhandi goats by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing","volume":"8","author":"Shrivastava","year":"2015","journal-title":"Vet. World"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7, Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.theriogenology.2013.03.008","article-title":"Transgenic cloned sheep overexpressing ovine toll-like receptor 4","volume":"80","author":"Deng","year":"2013","journal-title":"Theriogenology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1073\/pnas.70.12.3321","article-title":"Analysis of gene diversity in subdivided populations","volume":"70","author":"Nei","year":"1973","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3109\/23744235.2015.1016298","article-title":"TGF\u03b21 genetic variants are associated with an increased risk of acute brucellosis","volume":"47","author":"Sepanjnia","year":"2015","journal-title":"Infect. Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/10948\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:11Z","timestamp":1760112671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/20\/10948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,11]]},"references-count":65,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms252010948"],"URL":"https:\/\/doi.org\/10.3390\/ijms252010948","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,11]]}}}