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Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in ongoing programs toward controlling Mb infection. However, individual animal phenotypes for bTb based on interferon-gamma (IFN\u0263) and its use in bovine selective breeding programs have not been explored. In the current study, IFN\u0263 production was measured using a specific IFN\u0263 ELISA kit in bovine purified protein derivative (bPPD)-stimulated blood samples collected from Holstein cattle. DNA isolated from the peripheral blood samples collected from the animals included in the study was genotyped with the EuroG Medium Density bead Chip, and the genotypes were imputed to whole-genome sequences. A genome-wide association analysis (GWAS) revealed that the IFN\u0263 in response to bPPD was associated with a specific genetic profile (heritability = 0.23) and allowed the identification of 163 SNPs, 72 quantitative trait loci (QTLs), 197 candidate genes, and 8 microRNAs (miRNAs) associated with this phenotype. No negative correlations between this phenotype and other phenotypes and traits included in the Spanish breeding program were observed. Taken together, our results define a heritable and distinct immunogenetic profile associated with strong production of IFN\u0263 in response to Mb.<\/jats:p>","DOI":"10.3390\/ijms25116165","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T12:19:46Z","timestamp":1717417186000},"page":"6165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome-Wide Association Study Reveals Quantitative Trait Loci and Candidate Genes Associated with High Interferon-gamma Production in Holstein Cattle Naturally Infected with Mycobacterium Bovis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8943-2365","authenticated-orcid":false,"given":"Gerard","family":"Badia-Bringu\u00e9","sequence":"first","affiliation":[{"name":"Department of Animal Health, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Canive","sequence":"additional","affiliation":[{"name":"Department of Animal Health, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Animal Health, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseba M.","family":"Garrido","sequence":"additional","affiliation":[{"name":"Department of Animal Health, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Mejora Gen\u00e9tica Animal, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6037-5873","authenticated-orcid":false,"given":"Ram\u00f3n A.","family":"Juste","sequence":"additional","affiliation":[{"name":"Department of Animal Health, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8121-1509","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"CONAFE-Spanish Confederation of Holstein Cattle, 28340 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9106-4063","authenticated-orcid":false,"given":"Oscar","family":"Gonz\u00e1lez-Recio","sequence":"additional","affiliation":[{"name":"Departamento de Mejora Gen\u00e9tica Animal, Instituto Nacional de Investigaci\u00f3n y Tecnolog\u00eda Agraria y Alimentaria (INIA), 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5979-347X","authenticated-orcid":false,"given":"Marta","family":"Alonso-Hearn","sequence":"additional","affiliation":[{"name":"Department of Animal Health, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), 48160 Derio, Bizkaia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.prevetmed.2014.03.014","article-title":"Minimum Cost to Control Bovine Tuberculosis in Cow-Calf Herds","volume":"115","author":"Smith","year":"2014","journal-title":"Prev. 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