Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population
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{"title"=>"Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population", "type"=>"journal", "authors"=>[{"first_name"=>"Andrew K.", "last_name"=>"Turner", "scopus_author_id"=>"39661429200"}, {"first_name"=>"Mike", "last_name"=>"Begon", "scopus_author_id"=>"7006503936"}, {"first_name"=>"Joseph A.", "last_name"=>"Jackson", "scopus_author_id"=>"7404117014"}, {"first_name"=>"Janette E.", "last_name"=>"Bradley", "scopus_author_id"=>"7402239436"}, {"first_name"=>"Steve", "last_name"=>"Paterson", "scopus_author_id"=>"7102053189"}], "year"=>2011, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-80055080763", "pui"=>"362834395", "doi"=>"10.1371/journal.pgen.1002343", "isbn"=>"1553-7390\\r1553-7404", "sgr"=>"80055080763", "pmid"=>"22039363"}, "id"=>"77678bea-7be4-30a7-8e7f-12f76fc91fef", "abstract"=>"Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis) to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (Interleukin 1 beta (Il1b), Il2, and Il12b), rather than to other cytokines tested, or to membrane-bound, non-cytokine immune loci. The observed genetic effects were as great as for other intrinsic factors such as sex and body weight. Our results demonstrate that genetic diversity at cytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations. The products of these loci are therefore likely to affect interactions between pathogens and help determine survival and reproductive success in natural populations. Our study also highlights the utility of wild rodents as a model of ecological immunology, to better understand the causes and consequences of variation in immune function in natural populations including humans.", "link"=>"http://www.mendeley.com/research/genetic-diversity-cytokines-associated-immune-variation-resistance-multiple-pathogens-natural-rodent", "reader_count"=>96, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>6, "Student > Doctoral Student"=>5, "Researcher"=>27, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>3, "Student > Master"=>10, "Other"=>2, "Student > Bachelor"=>6, "Lecturer"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>6, "Student > Doctoral Student"=>5, "Researcher"=>27, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>3, "Student > Master"=>10, "Other"=>2, "Student > Bachelor"=>6, "Lecturer"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Environmental Science"=>4, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>66, "Medicine and Dentistry"=>4, "Design"=>1, "Veterinary Science and Veterinary Medicine"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Immunology and Microbiology"=>6}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>66}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>6}, "Environmental Science"=>{"Environmental Science"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>4}}, "reader_count_by_country"=>{"Canada"=>1, "Finland"=>1, "Poland"=>1, "South Africa"=>1, "United Kingdom"=>4, "Portugal"=>1, "Germany"=>1}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/721280"], "description"=>"a<p>Number of haplotypes sequenced.</p>b<p>Length of sequence (bp).</p>c<p>GenBank accession numbers for consensus sequences (including SNPs, designated using IUPAC ambiguity codes).</p><p>*We were unsuccessful in our attempts to amplify and sequence the following genes; <i>Il1a</i>, <i>Il4</i>, <i>Il12a</i> and <i>Il13</i>.</p>", "links"=>[], "tags"=>["sequenced", "vole"], "article_id"=>391640, "categories"=>["Microbiology", "Ecology", "Immunology", "Evolutionary Biology"], "users"=>["Andrew K. Turner", "Mike Begon", "Joseph A. Jackson", "Janette E. Bradley", "Steve Paterson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002343.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_sequenced_field_vole_immune_genes_/391640", "title"=>"Summary of sequenced field vole immune genes.<sup>*</sup>", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-20 00:27:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/721098"], "description"=>"<p>Arrows indicate where polymorphism within a gene is associated with variation in immune parameters (blue) or pathogen resistance (red). Solid arrows represent statistically significant associations (<i>p</i><0.05), dashed arrows represent marginally non-significant associations (0.05<<i>p</i><0.07). ‘Inf.’ refers to probability of infection and ‘bur.’ to parasite burden. <i>Il1b</i>, <i>Il2</i> and <i>Il12b</i> were consistently associated with variation in both immune parameters and resistance to multiple pathogens.</p>", "links"=>[], "tags"=>["diagram"], "article_id"=>391460, "categories"=>["Microbiology", "Ecology", "Immunology", "Evolutionary Biology"], "users"=>["Andrew K. Turner", "Mike Begon", "Joseph A. Jackson", "Janette E. Bradley", "Steve Paterson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002343.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_diagram_of_genetic_associations_/391460", "title"=>"Summary diagram of genetic associations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-20 00:24:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/721179"], "description"=>"a<p>Refers to cross-sectional (CS) or longitudinal (Long.) studies, which utilized GLMs and GLMMS, respectively, for analyses (see text).</p>b<p>Under an additive model, listed haplotypes were compared against the most common haplotype at that locus; under a heterozygosity model, values of heterozygotes were compared against homozygotes (see text).</p>c<p>Increment in AIC of the model if single term is dropped (GLMMs only).</p>d<p>Also significant under a heterozygosity model (ΔAIC = 2.1).</p>e<p>Also significant under a heterozygosity model (<i>p</i> = 0.043).</p>f<p>Also significant under a heterozygosity model (<i>p</i> = 0.007).</p><p>*<i>P</i>-values given for analyses using GLMMs are for equivalent GLMs.</p>", "links"=>[], "tags"=>["pathogen"], "article_id"=>391542, "categories"=>["Microbiology", "Ecology", "Immunology", "Evolutionary Biology"], "users"=>["Andrew K. Turner", "Mike Begon", "Joseph A. Jackson", "Janette E. Bradley", "Steve Paterson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002343.t004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_terms_significantly_associated_with_variation_in_pathogen_resistance_/391542", "title"=>"Genetic terms significantly associated with variation in pathogen resistance.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-20 00:25:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/721217"], "description"=>"a<p>Under an additive model, the range of effect sizes for alleles is shown compared against the most common haplotype at that locus; under a heterozygosity model, values of heterozygotes were compared against homozygotes (see text).</p>b<p>Effect size shown for comparative purposes based on the interquartile range for females within a single season (Spring 2008).</p>", "links"=>[], "tags"=>["sizes", "intrinsic", "immunological"], "article_id"=>391576, "categories"=>["Microbiology", "Ecology", "Immunology", "Evolutionary Biology"], "users"=>["Andrew K. Turner", "Mike Begon", "Joseph A. Jackson", "Janette E. Bradley", "Steve Paterson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002343.t003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_effect_sizes_for_genetic_versus_intrinsic_terms_in_immunological_parameters_/391576", "title"=>"Comparison of effect sizes for genetic versus intrinsic terms in immunological parameters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-20 00:26:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/721153"], "description"=>"a<p>Refers to cross-sectional (CS) or longitudinal (Long.) studies, which utilized GLMs and GLMMS, respectively, for analyses (see text).</p>b<p>Under an additive model, the range of effect sizes for alleles is shown compared against the most common haplotype at that locus; under a heterozygosity model, values of heterozygotes were compared against homozygotes (see text).</p>c<p>Effect size shown for comparative purposes based on the interquartile range for females within a single season (Spring 2008).</p>", "links"=>[], "tags"=>["sizes", "intrinsic", "pathogen"], "article_id"=>391513, "categories"=>["Microbiology", "Ecology", "Immunology", "Evolutionary Biology"], "users"=>["Andrew K. Turner", "Mike Begon", "Joseph A. Jackson", "Janette E. Bradley", "Steve Paterson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002343.t005", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_effect_sizes_for_genetic_versus_intrinsic_terms_in_pathogen_resistance_/391513", "title"=>"Comparison of effect sizes for genetic versus intrinsic terms in pathogen resistance.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-20 00:25:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/365107", "https://ndownloader.figshare.com/files/365149", "https://ndownloader.figshare.com/files/365195", "https://ndownloader.figshare.com/files/365221", "https://ndownloader.figshare.com/files/365274", "https://ndownloader.figshare.com/files/365316", "https://ndownloader.figshare.com/files/365391", "https://ndownloader.figshare.com/files/365448", "https://ndownloader.figshare.com/files/365519", "https://ndownloader.figshare.com/files/365563", "https://ndownloader.figshare.com/files/365610", "https://ndownloader.figshare.com/files/365667"], "description"=>"<div><p>Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (<em>Microtus agrestis</em>) to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (<em>Interleukin 1 beta</em> (<em>Il1b</em>), <em>Il2</em>, and <em>Il12b</em>), rather than to other cytokines tested, or to membrane-bound, non-cytokine immune loci. The observed genetic effects were as great as for other intrinsic factors such as sex and body weight. Our results demonstrate that genetic diversity at cytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations. The products of these loci are therefore likely to affect interactions between pathogens and help determine survival and reproductive success in natural populations. Our study also highlights the utility of wild rodents as a model of ecological immunology, to better understand the causes and consequences of variation in immune function in natural populations including humans.</p> </div>", "links"=>[], "tags"=>["cytokines", "pathogens", "rodent"], "article_id"=>132154, "categories"=>["Microbiology", "Ecology", "Immunology", "Evolutionary Biology"], "users"=>["Andrew K. Turner", "Mike Begon", "Joseph A. Jackson", "Janette E. Bradley", "Steve Paterson"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002343.s001", "https://dx.doi.org/10.1371/journal.pgen.1002343.s002", "https://dx.doi.org/10.1371/journal.pgen.1002343.s003", "https://dx.doi.org/10.1371/journal.pgen.1002343.s004", "https://dx.doi.org/10.1371/journal.pgen.1002343.s005", "https://dx.doi.org/10.1371/journal.pgen.1002343.s006", "https://dx.doi.org/10.1371/journal.pgen.1002343.s007", "https://dx.doi.org/10.1371/journal.pgen.1002343.s008", "https://dx.doi.org/10.1371/journal.pgen.1002343.s009", "https://dx.doi.org/10.1371/journal.pgen.1002343.s010", "https://dx.doi.org/10.1371/journal.pgen.1002343.s011", "https://dx.doi.org/10.1371/journal.pgen.1002343.s012"], "stats"=>{"downloads"=>7, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genetic_Diversity_in_Cytokines_Associated_with_Immune_Variation_and_Resistance_to_Multiple_Pathogens_in_a_Natural_Rodent_Population/132154", "title"=>"Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-10-20 00:35:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/721244"], "description"=>"a<p>Under an additive model, listed haplotypes were compared against the most common haplotype at that locus; under a heterozygosity model, values of heterozygotes were compared against homozygotes (see text).</p>b<p>Also significant under a heterozygosity model (<i>p</i> = 0.04).</p>c<p>Also significant under an additive model (<i>p</i> = 0.007).</p>", "links"=>[], "tags"=>["immunological"], "article_id"=>391610, "categories"=>["Microbiology", "Ecology", "Immunology", "Evolutionary Biology"], "users"=>["Andrew K. Turner", "Mike Begon", "Joseph A. Jackson", "Janette E. Bradley", "Steve Paterson"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002343.t002", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_terms_significantly_associated_with_variation_in_immunological_parameters_/391610", "title"=>"Genetic terms significantly associated with variation in immunological parameters.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-20 00:26:50"}

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