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Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array

BACKGROUND: Toll-like receptors (TLR) are crucial in innate immunity for the recognition of a broad range of microbial pathogens and are expressed in multiple cell types. There are 10 TLR genes described in the pig genome. RESULTS: With a twofold objective i.e. to catalogue genetic variants in porci...

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Autores principales: Clop, Alex, Huisman, Abe, van As, Pieter, Sharaf, Abdoallah, Derdak, Sophia, Sanchez, Armand
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818456/
https://www.ncbi.nlm.nih.gov/pubmed/27036198
http://dx.doi.org/10.1186/s12711-016-0206-0
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author Clop, Alex
Huisman, Abe
van As, Pieter
Sharaf, Abdoallah
Derdak, Sophia
Sanchez, Armand
author_facet Clop, Alex
Huisman, Abe
van As, Pieter
Sharaf, Abdoallah
Derdak, Sophia
Sanchez, Armand
author_sort Clop, Alex
collection PubMed
description BACKGROUND: Toll-like receptors (TLR) are crucial in innate immunity for the recognition of a broad range of microbial pathogens and are expressed in multiple cell types. There are 10 TLR genes described in the pig genome. RESULTS: With a twofold objective i.e. to catalogue genetic variants in porcine TLR genes and develop a genotyping array for genetic association studies on immune-related traits, we combined targeted sub-genome enrichment and high-throughput sequencing to sequence the 10 porcine TLR genes in 266 pigs from 10 breeds and wild boars using a DNA-pooling strategy. We identified 306 single nucleotide variants across the 10 TLR and 11 populations, 87 of which were novel. One hundred and forty-seven positions i.e. six stop-gains and 141 non-synonymous substitutions were predicted to alter the protein sequence. Three positions were unique to a single breed with alternative allele frequencies equal to or higher than 0.5. We designed a genotyping array for future applications in genetic association studies, with a selection of 126 variants based on their predicted impact on protein sequence. Since TLR4, TLR7 and TLR9 were underrepresented in this selection, we also included three variants that were located in the 3′UTR of these genes. We tested the array by genotyping 214 of the 266 sequenced pigs. We found that 93 variants that involved the 10 TLR genes were polymorphic in these animals. Twelve of these variants were novel. Furthermore, seven known variants that are associated with immune-related phenotypes are present on the array and can thus be used to test such associations in additional populations. CONCLUSIONS: We identified genetic variations that potentially have an impact on the protein sequence of porcine TLR. A genotyping array with 80 non-synonymous, 10 synonymous and three 3′UTR polymorphisms in the 10 TLR genes is now available for association studies in swine populations with measures on immune-related traits. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12711-016-0206-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-48184562016-04-03 Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array Clop, Alex Huisman, Abe van As, Pieter Sharaf, Abdoallah Derdak, Sophia Sanchez, Armand Genet Sel Evol Short Communication BACKGROUND: Toll-like receptors (TLR) are crucial in innate immunity for the recognition of a broad range of microbial pathogens and are expressed in multiple cell types. There are 10 TLR genes described in the pig genome. RESULTS: With a twofold objective i.e. to catalogue genetic variants in porcine TLR genes and develop a genotyping array for genetic association studies on immune-related traits, we combined targeted sub-genome enrichment and high-throughput sequencing to sequence the 10 porcine TLR genes in 266 pigs from 10 breeds and wild boars using a DNA-pooling strategy. We identified 306 single nucleotide variants across the 10 TLR and 11 populations, 87 of which were novel. One hundred and forty-seven positions i.e. six stop-gains and 141 non-synonymous substitutions were predicted to alter the protein sequence. Three positions were unique to a single breed with alternative allele frequencies equal to or higher than 0.5. We designed a genotyping array for future applications in genetic association studies, with a selection of 126 variants based on their predicted impact on protein sequence. Since TLR4, TLR7 and TLR9 were underrepresented in this selection, we also included three variants that were located in the 3′UTR of these genes. We tested the array by genotyping 214 of the 266 sequenced pigs. We found that 93 variants that involved the 10 TLR genes were polymorphic in these animals. Twelve of these variants were novel. Furthermore, seven known variants that are associated with immune-related phenotypes are present on the array and can thus be used to test such associations in additional populations. CONCLUSIONS: We identified genetic variations that potentially have an impact on the protein sequence of porcine TLR. A genotyping array with 80 non-synonymous, 10 synonymous and three 3′UTR polymorphisms in the 10 TLR genes is now available for association studies in swine populations with measures on immune-related traits. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12711-016-0206-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-03-31 /pmc/articles/PMC4818456/ /pubmed/27036198 http://dx.doi.org/10.1186/s12711-016-0206-0 Text en © Clop et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Communication
Clop, Alex
Huisman, Abe
van As, Pieter
Sharaf, Abdoallah
Derdak, Sophia
Sanchez, Armand
Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array
title Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array
title_full Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array
title_fullStr Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array
title_full_unstemmed Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array
title_short Identification of genetic variation in the swine toll-like receptors and development of a porcine TLR genotyping array
title_sort identification of genetic variation in the swine toll-like receptors and development of a porcine tlr genotyping array
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818456/
https://www.ncbi.nlm.nih.gov/pubmed/27036198
http://dx.doi.org/10.1186/s12711-016-0206-0
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