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Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar

Tuberculosis (TB) affects a wide range of host species worldwide. Understanding host-pathogen co-evolution remains a global challenge owing to complex interactions among host genetic factors, pathogen traits and environmental conditions. We used an endemic wild boar population that had undergone a h...

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Autores principales: Queirós, João, Alves, Paulo Célio, Vicente, Joaquín, Gortázar, Christian, de la Fuente, José
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792637/
https://www.ncbi.nlm.nih.gov/pubmed/29386541
http://dx.doi.org/10.1038/s41598-018-20158-x
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author Queirós, João
Alves, Paulo Célio
Vicente, Joaquín
Gortázar, Christian
de la Fuente, José
author_facet Queirós, João
Alves, Paulo Célio
Vicente, Joaquín
Gortázar, Christian
de la Fuente, José
author_sort Queirós, João
collection PubMed
description Tuberculosis (TB) affects a wide range of host species worldwide. Understanding host-pathogen co-evolution remains a global challenge owing to complex interactions among host genetic factors, pathogen traits and environmental conditions. We used an endemic wild boar population that had undergone a huge increase in Mycobacterium bovis infection prevalence, from 45% in 2002/06 to 83% in 2009/12, to understand the effects of host genetics on host TB outcomes and disease dynamics. Host genomic variation was characterized using a high-density single nucleotide polymorphism (SNP) array, while host TB phenotype was assessed using both gross pathology and mycobacterial culture. Two complementary genome-wide association (GWAS) analyses were conducted: (i) infected-uninfected; and (ii) 2002/06–2009/12. The SNPs with the highest allelic frequency differences between time-periods and TB outcomes were identified and validated in a large dataset. In addition, we quantified the expression levels of some of their closest genes. These analyses highlighted various SNPs (i.e. rs81465339, rs81394585, rs81423166) and some of the closest genes (i.e. LOC102164072, BDNF/NT-3, NTRK2, CDH8, IGSF21) as candidates for host genetic susceptibility. In addition to TB-driven selection, our findings outline the putative role of demographic events in shaping genomic variation in natural populations and how population crashes and drift may impact host genetic susceptibility to TB over time.
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spelling pubmed-57926372018-02-12 Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar Queirós, João Alves, Paulo Célio Vicente, Joaquín Gortázar, Christian de la Fuente, José Sci Rep Article Tuberculosis (TB) affects a wide range of host species worldwide. Understanding host-pathogen co-evolution remains a global challenge owing to complex interactions among host genetic factors, pathogen traits and environmental conditions. We used an endemic wild boar population that had undergone a huge increase in Mycobacterium bovis infection prevalence, from 45% in 2002/06 to 83% in 2009/12, to understand the effects of host genetics on host TB outcomes and disease dynamics. Host genomic variation was characterized using a high-density single nucleotide polymorphism (SNP) array, while host TB phenotype was assessed using both gross pathology and mycobacterial culture. Two complementary genome-wide association (GWAS) analyses were conducted: (i) infected-uninfected; and (ii) 2002/06–2009/12. The SNPs with the highest allelic frequency differences between time-periods and TB outcomes were identified and validated in a large dataset. In addition, we quantified the expression levels of some of their closest genes. These analyses highlighted various SNPs (i.e. rs81465339, rs81394585, rs81423166) and some of the closest genes (i.e. LOC102164072, BDNF/NT-3, NTRK2, CDH8, IGSF21) as candidates for host genetic susceptibility. In addition to TB-driven selection, our findings outline the putative role of demographic events in shaping genomic variation in natural populations and how population crashes and drift may impact host genetic susceptibility to TB over time. Nature Publishing Group UK 2018-01-31 /pmc/articles/PMC5792637/ /pubmed/29386541 http://dx.doi.org/10.1038/s41598-018-20158-x Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Queirós, João
Alves, Paulo Célio
Vicente, Joaquín
Gortázar, Christian
de la Fuente, José
Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
title Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
title_full Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
title_fullStr Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
title_full_unstemmed Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
title_short Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
title_sort genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792637/
https://www.ncbi.nlm.nih.gov/pubmed/29386541
http://dx.doi.org/10.1038/s41598-018-20158-x
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