Cargando…

Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection

Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specif...

Descripción completa

Detalles Bibliográficos
Autores principales: Fisher, Colleen A., Bhattarai, Eric K., Osterstock, Jason B., Dowd, Scot E., Seabury, Paul M., Vikram, Meenu, Whitlock, Robert H., Schukken, Ynte H., Schnabel, Robert D., Taylor, Jeremy F., Womack, James E., Seabury, Christopher M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227585/
https://www.ncbi.nlm.nih.gov/pubmed/22164200
http://dx.doi.org/10.1371/journal.pone.0027744
_version_ 1782217761363066880
author Fisher, Colleen A.
Bhattarai, Eric K.
Osterstock, Jason B.
Dowd, Scot E.
Seabury, Paul M.
Vikram, Meenu
Whitlock, Robert H.
Schukken, Ynte H.
Schnabel, Robert D.
Taylor, Jeremy F.
Womack, James E.
Seabury, Christopher M.
author_facet Fisher, Colleen A.
Bhattarai, Eric K.
Osterstock, Jason B.
Dowd, Scot E.
Seabury, Paul M.
Vikram, Meenu
Whitlock, Robert H.
Schukken, Ynte H.
Schnabel, Robert D.
Taylor, Jeremy F.
Womack, James E.
Seabury, Christopher M.
author_sort Fisher, Colleen A.
collection PubMed
description Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and specialized beef and dairy breeds could not be differentiated despite an average polymorphism density of 1 marker/158 bp. Collectively, 160 tagSNPs and two tag insertion-deletion mutations (indels) were sufficient to predict 100% of the variation at 280 variable sites for both Bos subspecies and their hybrids, whereas 118 tagSNPs and 1 tagIndel predictively captured 100% of the variation at 235 variable sites for B. t. taurus. Polyphen and SIFT analyses of amino acid (AA) replacements encoded by bovine TLR SNPs indicated that up to 32% of the AA substitutions were expected to impact protein function. Classical and newly developed tests of diversity provide strong support for balancing selection operating on TLR3 and TLR8, and purifying selection acting on TLR10. An investigation of the persistence and continuity of linkage disequilibrium (r(2)≥0.50) between adjacent variable sites also supported the presence of selection acting on TLR3 and TLR8. A case-control study employing validated variants from bovine TLR genes recognizing bacterial ligands revealed six SNPs potentially eliciting small effects on susceptibility to Mycobacterium avium spp paratuberculosis infection in dairy cattle. The results of this study will broadly impact domestic cattle research by providing the necessary foundation to explore several avenues of bovine translational genomics, and the potential for marker-assisted vaccination.
format Online
Article
Text
id pubmed-3227585
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-32275852011-12-07 Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection Fisher, Colleen A. Bhattarai, Eric K. Osterstock, Jason B. Dowd, Scot E. Seabury, Paul M. Vikram, Meenu Whitlock, Robert H. Schukken, Ynte H. Schnabel, Robert D. Taylor, Jeremy F. Womack, James E. Seabury, Christopher M. PLoS One Research Article Members of the Toll-like receptor (TLR) gene family occupy key roles in the mammalian innate immune system by functioning as sentries for the detection of invading pathogens, thereafter provoking host innate immune responses. We utilized a custom next-generation sequencing approach and allele-specific genotyping assays to detect and validate 280 biallelic variants across all 10 bovine TLR genes, including 71 nonsynonymous single nucleotide polymorphisms (SNPs) and one putative nonsense SNP. Bayesian haplotype reconstructions and median joining networks revealed haplotype sharing between Bos taurus taurus and Bos taurus indicus breeds at every locus, and specialized beef and dairy breeds could not be differentiated despite an average polymorphism density of 1 marker/158 bp. Collectively, 160 tagSNPs and two tag insertion-deletion mutations (indels) were sufficient to predict 100% of the variation at 280 variable sites for both Bos subspecies and their hybrids, whereas 118 tagSNPs and 1 tagIndel predictively captured 100% of the variation at 235 variable sites for B. t. taurus. Polyphen and SIFT analyses of amino acid (AA) replacements encoded by bovine TLR SNPs indicated that up to 32% of the AA substitutions were expected to impact protein function. Classical and newly developed tests of diversity provide strong support for balancing selection operating on TLR3 and TLR8, and purifying selection acting on TLR10. An investigation of the persistence and continuity of linkage disequilibrium (r(2)≥0.50) between adjacent variable sites also supported the presence of selection acting on TLR3 and TLR8. A case-control study employing validated variants from bovine TLR genes recognizing bacterial ligands revealed six SNPs potentially eliciting small effects on susceptibility to Mycobacterium avium spp paratuberculosis infection in dairy cattle. The results of this study will broadly impact domestic cattle research by providing the necessary foundation to explore several avenues of bovine translational genomics, and the potential for marker-assisted vaccination. Public Library of Science 2011-11-30 /pmc/articles/PMC3227585/ /pubmed/22164200 http://dx.doi.org/10.1371/journal.pone.0027744 Text en Fisher et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fisher, Colleen A.
Bhattarai, Eric K.
Osterstock, Jason B.
Dowd, Scot E.
Seabury, Paul M.
Vikram, Meenu
Whitlock, Robert H.
Schukken, Ynte H.
Schnabel, Robert D.
Taylor, Jeremy F.
Womack, James E.
Seabury, Christopher M.
Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection
title Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection
title_full Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection
title_fullStr Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection
title_full_unstemmed Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection
title_short Evolution of the Bovine TLR Gene Family and Member Associations with Mycobacterium avium Subspecies paratuberculosis Infection
title_sort evolution of the bovine tlr gene family and member associations with mycobacterium avium subspecies paratuberculosis infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227585/
https://www.ncbi.nlm.nih.gov/pubmed/22164200
http://dx.doi.org/10.1371/journal.pone.0027744
work_keys_str_mv AT fishercolleena evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT bhattaraierick evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT osterstockjasonb evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT dowdscote evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT seaburypaulm evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT vikrammeenu evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT whitlockroberth evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT schukkenynteh evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT schnabelrobertd evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT taylorjeremyf evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT womackjamese evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection
AT seaburychristopherm evolutionofthebovinetlrgenefamilyandmemberassociationswithmycobacteriumaviumsubspeciesparatuberculosisinfection