Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA) Gene
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{"title"=>"Dominant red coat color in Holstein cattle is associated with a missense mutation in the coatomer protein complex, subunit alpha (COPA) gene", "type"=>"journal", "authors"=>[{"first_name"=>"Ben", "last_name"=>"Dorshorst", "scopus_author_id"=>"34869518200"}, {"first_name"=>"Corneliu", "last_name"=>"Henegar", "scopus_author_id"=>"23012382400"}, {"first_name"=>"Xiaoping", "last_name"=>"Liao", "scopus_author_id"=>"46061560300"}, {"first_name"=>"Markus Sällman", "last_name"=>"Almén", "scopus_author_id"=>"26667507600"}, {"first_name"=>"Carl Johan", "last_name"=>"Rubin", "scopus_author_id"=>"57198110901"}, {"first_name"=>"Shosuke", "last_name"=>"Ito", "scopus_author_id"=>"7404826072"}, {"first_name"=>"Kazumasa", "last_name"=>"Wakamatsu", "scopus_author_id"=>"7102008426"}, {"first_name"=>"Paul", "last_name"=>"Stothard", "scopus_author_id"=>"6601960208"}, {"first_name"=>"Brian", "last_name"=>"Van Doormaal", "scopus_author_id"=>"6603372211"}, {"first_name"=>"Graham", "last_name"=>"Plastow", "scopus_author_id"=>"6701744332"}, {"first_name"=>"Gregory S.", "last_name"=>"Barsh", "scopus_author_id"=>"35394756500"}, {"first_name"=>"Leif", "last_name"=>"Andersson", "scopus_author_id"=>"7403057299"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84934922287", "doi"=>"10.1371/journal.pone.0128969", "pmid"=>"26042826", "issn"=>"19326203", "scopus"=>"2-s2.0-84934922287", "pui"=>"604911835"}, "id"=>"d15c52b4-d923-366c-aed5-bf3e9b74b623", "abstract"=>"Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins are Dominant Black (MC1RD) and Recessive Red (MC1Re). A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named Dominant Red and is epistatic to the constitutively activated MC1RD. Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle. The mutation results in an arginine to cysteine substitution at an amino acid residue completely conserved across eukaryotes. Despite this high level of conservation we show that both heterozygotes and homozygotes are healthy and viable. Analysis of hair pigment composition shows that the Dominant Red phenotype is similar to the MC1R Recessive Red phenotype, although less effective at reducing eumelanin synthesis. RNA-seq data similarly show that Dominant Red animals achieve predominantly pheomelanin synthesis by downregulating genes normally required for eumelanin synthesis. COPA is a component of the coat protein I seven subunit complex that is involved with retrograde and cis-Golgi intracellular coated vesicle transport of both protein and RNA cargo. This suggests that Dominant Red may be caused by aberrant MC1R protein or mRNA trafficking within the highly compartmentalized melanocyte, mimicking the effect of the Recessive Red loss of function MC1R allele.", "link"=>"http://www.mendeley.com/research/dominant-red-coat-color-holstein-cattle-associated-missense-mutation-coatomer-protein-complex-subuni", "reader_count"=>28, "reader_count_by_academic_status"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Agricultural and Biological Sciences"=>20, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"New Zealand"=>1, "Argentina"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2095779"], "description"=>"<p>Standard error in italics below respective mean.</p><p><sup>A B C</sup> Means with significant difference (<i>P</i><0.05) indicated by different superscript letters.</p><p>Hair pigment content and composition.</p>", "links"=>[], "tags"=>["MC 1RD", "hair pigment composition", "MC 1R alleles", "Gene Coat color", "Dominant Red animals", "function MC 1R allele", "Holstein dairy cattle", "Dominant Red", "eumelanin synthesis", "Melanocortin 1 receptor", "MC 1R Recessive Red phenotype", "Dominant Red Coat Color", "MC 1R gene", "Coatomer Protein Complex", "MC 1R protein", "rna", "Recessive Red loss", "copa", "Dominant Red phenotype"], "article_id"=>1436745, "categories"=>["Biological Sciences"], "users"=>["Ben Dorshorst", "Corneliu Henegar", "Xiaoping Liao", "Markus Sällman Almén", "Carl-Johan Rubin", "Shosuke Ito", "Kazumasa Wakamatsu", "Paul Stothard", "Brian Van Doormaal", "Graham Plastow", "Gregory S. Barsh", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128969.t001", "stats"=>{"downloads"=>3, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hair_pigment_content_and_composition_/1436745", "title"=>"Hair pigment content and composition.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-04 03:12:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2095777"], "description"=>"<p>Multiple sequence alignment using MUSCLE [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0128969#pone.0128969.ref016\" target=\"_blank\">16</a>] of COPA and orthologues indicates high conservation across 17 species from mammals to yeast. The arginine (R) to cysteine (C) amino acid substitution caused by the Dominant Red SNP is indicated with the arrow and is completely conserved in all species with available sequences. The WD40 repeat motif is highlighted in yellow.</p>", "links"=>[], "tags"=>["MC 1RD", "hair pigment composition", "MC 1R alleles", "Gene Coat color", "Dominant Red animals", "function MC 1R allele", "Holstein dairy cattle", "Dominant Red", "eumelanin synthesis", "Melanocortin 1 receptor", "MC 1R Recessive Red phenotype", "Dominant Red Coat Color", "MC 1R gene", "Coatomer Protein Complex", "MC 1R protein", "rna", "Recessive Red loss", "copa", "Dominant Red phenotype"], "article_id"=>1436743, "categories"=>["Biological Sciences"], "users"=>["Ben Dorshorst", "Corneliu Henegar", "Xiaoping Liao", "Markus Sällman Almén", "Carl-Johan Rubin", "Shosuke Ito", "Kazumasa Wakamatsu", "Paul Stothard", "Brian Van Doormaal", "Graham Plastow", "Gregory S. Barsh", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128969.g003", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evolutionary_conservation_of_Dominant_Red_associated_COPA_mutation_/1436743", "title"=>"Evolutionary conservation of Dominant Red associated COPA mutation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-04 03:12:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2095778"], "description"=>"<p>Gene expression levels (normalized gene counts averaged across the six analyzed samples) are represented as a function of log2-fold changes of Dominant Red versus Dominant Black samples. Genes that are significantly overexpressed in Dominant Black skin samples are depicted in black, those overexpressed in Dominant Red samples are illustrated in red, while non-significant changes are illustrated in gray. Genes previously implicated in melanocyte biology and/or pigment type-switching are annotated (selected genes that do not exhibit a significant difference at FDR<0.1 are highlighted in blue while the ones showing significant expression changes are marked additionally with an asterisk associated to the gene symbol).</p>", "links"=>[], "tags"=>["MC 1RD", "hair pigment composition", "MC 1R alleles", "Gene Coat color", "Dominant Red animals", "function MC 1R allele", "Holstein dairy cattle", "Dominant Red", "eumelanin synthesis", "Melanocortin 1 receptor", "MC 1R Recessive Red phenotype", "Dominant Red Coat Color", "MC 1R gene", "Coatomer Protein Complex", "MC 1R protein", "rna", "Recessive Red loss", "copa", "Dominant Red phenotype"], "article_id"=>1436744, "categories"=>["Biological Sciences"], "users"=>["Ben Dorshorst", "Corneliu Henegar", "Xiaoping Liao", "Markus Sällman Almén", "Carl-Johan Rubin", "Shosuke Ito", "Kazumasa Wakamatsu", "Paul Stothard", "Brian Van Doormaal", "Graham Plastow", "Gregory S. Barsh", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128969.g004", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differential_expression_results_comparing_Dominant_Red_DR_DR_DR__MC1R_D_MC1R_D_and_Dominant_Black_DR_DR__MC1R_D_skin_samples_/1436744", "title"=>"Differential expression results comparing Dominant Red (<i>DR</i><sup><i>DR</i></sup><i>/DR</i><sup><i>+</i></sup>, <i>MC1R</i><sup><i>D</i></sup><i>/MC1R</i><sup><i>D</i></sup>) and Dominant Black (<i>DR</i><sup><i>+</i></sup><i>/DR</i><sup><i>+</i></sup>, <i>MC1R</i><sup><i>D</i></sup><i>/-</i>) skin samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-04 03:12:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2095776"], "description"=>"<p>(A) Whole genome linkage mapping using a single half-sib family of 15 DR and 17 WT animals shows Dominant Red is located on BTA3. The black line is a cubic spline smoother with a lambda of 0.05. (B) Linkage mapping shows eight contiguous SNPs on BTA3 in complete association with Dominant Red across a 10.7 Mb region. (C) Genome-wide association analysis in 95 DR and more than 500 WT animals identifies a significant association on BTA3 within the 10.7 Mb region identified by linkage mapping. The most significant marker is ARS-BFGL-NGS-94819 @ 9,722,400 bp. The black line is a cubic spline smoother with a lambda of 0.05.</p>", "links"=>[], "tags"=>["MC 1RD", "hair pigment composition", "MC 1R alleles", "Gene Coat color", "Dominant Red animals", "function MC 1R allele", "Holstein dairy cattle", "Dominant Red", "eumelanin synthesis", "Melanocortin 1 receptor", "MC 1R Recessive Red phenotype", "Dominant Red Coat Color", "MC 1R gene", "Coatomer Protein Complex", "MC 1R protein", "rna", "Recessive Red loss", "copa", "Dominant Red phenotype"], "article_id"=>1436742, "categories"=>["Biological Sciences"], "users"=>["Ben Dorshorst", "Corneliu Henegar", "Xiaoping Liao", "Markus Sällman Almén", "Carl-Johan Rubin", "Shosuke Ito", "Kazumasa Wakamatsu", "Paul Stothard", "Brian Van Doormaal", "Graham Plastow", "Gregory S. Barsh", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128969.g002", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Linkage_and_genome_wide_association_mapping_of_Dominant_Red_/1436742", "title"=>"Linkage and genome-wide association mapping of Dominant Red.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-04 03:12:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2095780"], "description"=>"<p>KEGG pathways significantly enriched in genes that are overexpressed in Dominant Red skin samples.</p>", "links"=>[], "tags"=>["MC 1RD", "hair pigment composition", "MC 1R alleles", "Gene Coat color", "Dominant Red animals", "function MC 1R allele", "Holstein dairy cattle", "Dominant Red", "eumelanin synthesis", "Melanocortin 1 receptor", "MC 1R Recessive Red phenotype", "Dominant Red Coat Color", "MC 1R gene", "Coatomer Protein Complex", "MC 1R protein", "rna", "Recessive Red loss", "copa", "Dominant Red phenotype"], "article_id"=>1436746, "categories"=>["Biological Sciences"], "users"=>["Ben Dorshorst", "Corneliu Henegar", "Xiaoping Liao", "Markus Sällman Almén", "Carl-Johan Rubin", "Shosuke Ito", "Kazumasa Wakamatsu", "Paul Stothard", "Brian Van Doormaal", "Graham Plastow", "Gregory S. Barsh", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128969.t002", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_KEGG_pathways_significantly_enriched_in_genes_that_are_overexpressed_in_Dominant_Red_skin_samples_/1436746", "title"=>"KEGG pathways significantly enriched in genes that are overexpressed in Dominant Red skin samples.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-04 03:12:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2095775"], "description"=>"<p>(A) The first animal to display the Dominant Red phenotype was SURINAM SHEIK ROSABEL-RED (HOCANF3541221), born in 1980 in Ontario Canada. (B) A Dominant Black Holstein female. (C) A Recessive Red Holstein female. (D) A Dominant Red Holstein female. Reprinted under a CC BY license, with permission from (A) Canadian Livestock Photography Inc., original copyright 1985 and (B, C and D) Cybil Fisher Photography, original copyright 2014.</p>", "links"=>[], "tags"=>["MC 1RD", "hair pigment composition", "MC 1R alleles", "Gene Coat color", "Dominant Red animals", "function MC 1R allele", "Holstein dairy cattle", "Dominant Red", "eumelanin synthesis", "Melanocortin 1 receptor", "MC 1R Recessive Red phenotype", "Dominant Red Coat Color", "MC 1R gene", "Coatomer Protein Complex", "MC 1R protein", "rna", "Recessive Red loss", "copa", "Dominant Red phenotype"], "article_id"=>1436741, "categories"=>["Biological Sciences"], "users"=>["Ben Dorshorst", "Corneliu Henegar", "Xiaoping Liao", "Markus Sällman Almén", "Carl-Johan Rubin", "Shosuke Ito", "Kazumasa Wakamatsu", "Paul Stothard", "Brian Van Doormaal", "Graham Plastow", "Gregory S. Barsh", "Leif Andersson"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0128969.g001", "stats"=>{"downloads"=>2, "page_views"=>80, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dominant_Red_DR_DR_DR_MC1R_D__Dominant_Black_DR_DR_MC1R_D_and_Recessive_Red_DR_DR_MC1R_e_MC1R_e_phenotypes_/1436741", "title"=>"Dominant Red (<i>DR</i><sup><i>DR</i></sup><i>/DR</i><sup><i>+</i></sup>, MC1R<sup><i>D</i></sup><i>/-</i>), Dominant Black (<i>DR</i><sup><i>+</i></sup><i>/DR</i><sup><i>+</i></sup>, MC1R<sup><i>D</i></sup><i>/-</i>) and Recessive Red (<i>DR</i><sup><i>+</i></sup><i>/DR</i><sup><i>+</i></sup>, MC1R<sup><i>e</i></sup><i>/MC1R</i><sup><i>e</i></sup>) phenotypes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-04 03:12:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2095821", "https://ndownloader.figshare.com/files/2095823", "https://ndownloader.figshare.com/files/2095824", "https://ndownloader.figshare.com/files/2095825"], "description"=>"<div><p>Coat color in Holstein dairy cattle is primarily controlled by the <i>melanocortin 1 receptor</i> (<i>MC1R</i>) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species. The major <i>MC1R</i> alleles in Holsteins are Dominant <i>Black</i> (<i>MC1R<sup>D</sup></i>) and <i>Recessive Red</i> (<i>MC1R<sup>e</sup></i>). A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named <i>Dominant Red</i> and is epistatic to the constitutively activated <i>MC1R<sup>D</sup></i>. Here we show that a missense mutation in the <i>coatomer protein complex</i>, <i>subunit alpha</i> (<i>COPA</i>), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle. The mutation results in an arginine to cysteine substitution at an amino acid residue completely conserved across eukaryotes. Despite this high level of conservation we show that both heterozygotes and homozygotes are healthy and viable. Analysis of hair pigment composition shows that the Dominant Red phenotype is similar to the <i>MC1R</i> Recessive Red phenotype, although less effective at reducing eumelanin synthesis. RNA-seq data similarly show that Dominant Red animals achieve predominantly pheomelanin synthesis by downregulating genes normally required for eumelanin synthesis. COPA is a component of the coat protein I seven subunit complex that is involved with retrograde and cis-Golgi intracellular coated vesicle transport of both protein and RNA cargo. This suggests that Dominant Red may be caused by aberrant MC1R protein or mRNA trafficking within the highly compartmentalized melanocyte, mimicking the effect of the Recessive Red loss of function <i>MC1R</i> allele.</p></div>", "links"=>[], "tags"=>["MC 1RD", "hair pigment composition", "MC 1R alleles", "Gene Coat color", "Dominant Red animals", "function MC 1R allele", "Holstein dairy cattle", "Dominant Red", "eumelanin synthesis", "Melanocortin 1 receptor", "MC 1R Recessive Red phenotype", "Dominant Red Coat Color", "MC 1R gene", "Coatomer Protein Complex", "MC 1R protein", "rna", "Recessive Red loss", "copa", "Dominant Red phenotype"], "article_id"=>1436787, "categories"=>["Biological Sciences"], "users"=>["Ben Dorshorst", "Corneliu Henegar", "Xiaoping Liao", "Markus Sällman Almén", "Carl-Johan Rubin", "Shosuke Ito", "Kazumasa Wakamatsu", "Paul Stothard", "Brian Van Doormaal", "Graham Plastow", "Gregory S. Barsh", "Leif Andersson"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0128969.s001", "https://dx.doi.org/10.1371/journal.pone.0128969.s002", "https://dx.doi.org/10.1371/journal.pone.0128969.s003", "https://dx.doi.org/10.1371/journal.pone.0128969.s004"], "stats"=>{"downloads"=>4, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dominant_Red_Coat_Color_in_Holstein_Cattle_Is_Associated_with_a_Missense_Mutation_in_the_Coatomer_Protein_Complex_Subunit_Alpha_COPA_Gene/1436787", "title"=>"Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha <i>(COPA)</i> Gene", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-04 03:12:22"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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