Identification of loci associated with pathological outcomes in Holstein cattle infected with Mycobacterium avium subsp. paratuberculosis using whole-genome sequence data
dc.contributor.author | Canive Ruiz, María | |
dc.contributor.author | Badia Bringué, Gerard | |
dc.contributor.author | Vázquez, Patricia | |
dc.contributor.author | González Recio, Oscar | |
dc.contributor.author | Fernández, Almudena | |
dc.contributor.author | Garrido Urkullu, Joseba M. | |
dc.contributor.author | Juste Jordán, Ramón A. | |
dc.contributor.author | Alonso Hearn, Marta | |
dc.date.accessioned | 2021-11-17T08:30:30Z | |
dc.date.available | 2021-11-17T08:30:30Z | |
dc.date.issued | 2021-10-11 | |
dc.identifier.citation | Scientific Reports 11(1) : (2021) // Article ID 20177 | es_ES |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10810/53777 | |
dc.description.abstract | [EN]Bovine paratuberculosis (PTB), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis that affects cattle worldwide. According to their severity and extension, PTB-associated histological lesions have been classified into the following groups; focal, multifocal, and diffuse. It is unknown whether these lesions represent sequential stages or divergent outcomes. In the current study, the associations between host genetic and pathology were explored by genotyping 813 Spanish Holstein cows with no visible lesions (N = 373) and with focal (N = 371), multifocal (N = 33), and diffuse (N = 33) lesions in gut tissues and regional lymph nodes. DNA from peripheral blood samples of these animals was genotyped with the bovine EuroG MD Bead Chip, and the corresponding genotypes were imputed to whole-genome sequencing (WGS) data using the 1000 Bull genomes reference population. A genome-wide association study (GWAS) was performed using the WGS data and the presence or absence of each type of histological lesion in a case-control approach. A total of 192 and 92 single nucleotide polymorphisms (SNPs) defining 13 and 9 distinct quantitative trait loci (QTLs) were highly-associated (P <= 5 x 10(-7)) with the multifocal (heritability = 0.075) and the diffuse (heritability = 0.189) lesions, respectively. No overlap was seen in the SNPs controlling these distinct pathological outcomes. The identified QTLs overlapped with some QTLs previously associated with PTB susceptibility, bovine tuberculosis susceptibility, clinical mastitis, somatic cell score, bovine respiratory disease susceptibility, tick resistance, IgG level, and length of productive life. Pathway analysis with candidate genes overlapping the identified QTLs revealed a significant enrichment of the keratinization pathway and cholesterol metabolism in the animals with multifocal and diffuse lesions, respectively. To test whether the enrichment of SNP variants in candidate genes involved in the cholesterol metabolism was associated with the diffuse lesions; the levels of total cholesterol were measured in plasma samples of cattle with focal, multifocal, or diffuse lesions or with no visible lesions. Our results showed reduced levels of plasma cholesterol in cattle with diffuse lesions. Taken together, our findings suggested that the variation in MAP-associated pathological outcomes might be, in part, genetically determined and indicative of distinct host responses. | es_ES |
dc.description.sponsorship | Financial support for this study was provided by a Grant from the Spanish Ministry of Science, Innovation, and Universities (RTI2018-094192-R-C21) and by European Regional Development Funds (FEDER) to MAH. MC and GBB have been awarded fellowships from the National Institute for Agricultural Research (INIA) and the Spanish Ministry of Science, Innovation and Universities programs, respectively. This work has been possible thanks to the support of the computing infrastructure of the i2BASQUE Research and Academic Network. We gratefully acknowledge the Bull Genomes Consortium for providing accessibility to the WGS data that was used in this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Research | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-094192-R-C21 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | quantitative trait loci | es_ES |
dc.subject | wide association | es_ES |
dc.subject | r-package | es_ES |
dc.subject | susceptibility | es_ES |
dc.subject | disease | es_ES |
dc.subject | mastitis | es_ES |
dc.subject | tissue | es_ES |
dc.title | Identification of loci associated with pathological outcomes in Holstein cattle infected with Mycobacterium avium subsp. paratuberculosis using whole-genome sequence data | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | his article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41598-021-99672-4 | es_ES |
dc.identifier.doi | 10.1038/s41598-021-99672-4 | |
dc.departamentoes | Inmunología, microbiología y parasitología | es_ES |
dc.departamentoeu | Immunologia, mikrobiologia eta parasitologia | es_ES |
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