Genome Wide Association Analysis of a Founder Population Identified TAF3 as a Gene for MCHC in Humans
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{"title"=>"Genome Wide Association Analysis of a Founder Population Identified TAF3 as a Gene for MCHC in Humans", "type"=>"journal", "authors"=>[{"first_name"=>"Giorgio", "last_name"=>"Pistis", "scopus_author_id"=>"55335746300"}, {"first_name"=>"Shawntel U.", "last_name"=>"Okonkwo", "scopus_author_id"=>"55813351800"}, {"first_name"=>"Michela", "last_name"=>"Traglia", "scopus_author_id"=>"35173670400"}, {"first_name"=>"Cinzia", "last_name"=>"Sala", "scopus_author_id"=>"55336139100"}, {"first_name"=>"So Youn", "last_name"=>"Shin", "scopus_author_id"=>"37098955800"}, {"first_name"=>"Corrado", "last_name"=>"Masciullo", "scopus_author_id"=>"35173411200"}, {"first_name"=>"Iwan", "last_name"=>"Buetti", "scopus_author_id"=>"22953152200"}, {"first_name"=>"Roberto", "last_name"=>"Massacane", "scopus_author_id"=>"7801612777"}, {"first_name"=>"Massimo", "last_name"=>"Mangino", "scopus_author_id"=>"15926160500"}, {"first_name"=>"Swee Lay", "last_name"=>"Thein", "scopus_author_id"=>"55954889600"}, {"first_name"=>"Timothy D.", "last_name"=>"Spector", "scopus_author_id"=>"35351391300"}, {"first_name"=>"Santhi", "last_name"=>"Ganesh", "scopus_author_id"=>"12766425900"}, {"first_name"=>"Nicola", "last_name"=>"Pirastu", "scopus_author_id"=>"22635433900"}, {"first_name"=>"Paolo", "last_name"=>"Gasparini", "scopus_author_id"=>"22634397400"}, {"first_name"=>"Nicole", "last_name"=>"Soranzo", "scopus_author_id"=>"55800239500"}, {"first_name"=>"Clara", "last_name"=>"Camaschella", "scopus_author_id"=>"16206460600"}, {"first_name"=>"Daniel", "last_name"=>"Hart", "scopus_author_id"=>"35302429900"}, {"first_name"=>"Michael R.", "last_name"=>"Green", "scopus_author_id"=>"55628582845"}, {"first_name"=>"Daniela", "last_name"=>"Toniolo", "scopus_author_id"=>"7007056058"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84881164024", "pmid"=>"23935956", "sgr"=>"84881164024", "doi"=>"10.1371/journal.pone.0069206", "isbn"=>"2200820186", "issn"=>"19326203", "pui"=>"369507700"}, "id"=>"ceee66e8-53f8-35dd-ab65-024279ca7c30", "abstract"=>"The red blood cell related traits are highly heritable but their genetics are poorly defined. Only 5-10% of the total observed variance is explained by the genetic loci found to date, suggesting that additional loci should be searched using approaches alternative to large meta analysis. GWAS (Genome Wide Association Study) for red blood cell traits in a founder population cohort from Northern Italy identified a new locus for mean corpuscular hemoglobin concentration (MCHC) in the TAF3 gene. The association was replicated in two cohorts (rs1887582, P = 4.25E-09). TAF3 encodes a transcription cofactor that participates in core promoter recognition complex, and is involved in zebrafish and mouse erythropoiesis. We show here that TAF3 is required for transcription of the SPTA1 gene, encoding alpha spectrin, one of the proteins that link the plasma membrane to the actin cytoskeleton. Mutations in SPTA1 are responsible for hereditary spherocytosis, a monogenic disorder of MCHC, as well as for the normal MCHC level. Based on our results, we propose that TAF3 is required for normal erythropoiesis in human and that it might have a role in controlling the ratio between hemoglobin (Hb) and cell volume and in the dynamics of RBC maturation in healthy individuals. Finally, TAF3 represents a potential candidate or a modifier gene for disorders of red cell membrane.", "link"=>"http://www.mendeley.com/research/genome-wide-association-analysis-founder-population-identified-taf3-gene-mchc-humans", "reader_count"=>10, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Other"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Other"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Mathematics"=>1, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1138729", "https://ndownloader.figshare.com/files/1138732", "https://ndownloader.figshare.com/files/1138736", "https://ndownloader.figshare.com/files/1138739", "https://ndownloader.figshare.com/files/1138744", "https://ndownloader.figshare.com/files/1138747", "https://ndownloader.figshare.com/files/1138750"], "description"=>"<div><p>The red blood cell related traits are highly heritable but their genetics are poorly defined. Only 5–10% of the total observed variance is explained by the genetic loci found to date, suggesting that additional loci should be searched using approaches alternative to large meta analysis. GWAS (Genome Wide Association Study) for red blood cell traits in a founder population cohort from Northern Italy identified a new locus for mean corpuscular hemoglobin concentration (MCHC) in the <i>TAF3</i> gene. The association was replicated in two cohorts (rs1887582, <i>P</i> = 4.25E–09). <i>TAF3</i> encodes a transcription cofactor that participates in core promoter recognition complex, and is involved in zebrafish and mouse erythropoiesis. We show here that TAF3 is required for transcription of the <i>SPTA1</i> gene, encoding alpha spectrin, one of the proteins that link the plasma membrane to the actin cytoskeleton. Mutations in S<i>PTA1</i> are responsible for hereditary spherocytosis, a monogenic disorder of MCHC, as well as for the normal MCHC level. Based on our results, we propose that <i>TAF3</i> is required for normal erythropoiesis in human and that it might have a role in controlling the ratio between hemoglobin (Hb) and cell volume and in the dynamics of RBC maturation in healthy individuals. Finally, <i>TAF3</i> represents a potential candidate or a modifier gene for disorders of red cell membrane.</p></div>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "Genome-wide association studies", "Molecular cell biology", "Cellular structures", "cytoskeleton", "hematology", "anemia", "hematopoiesis", "Red cells", "genome", "mchc", "humans"], "article_id"=>761083, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Giorgio Pistis", "Shawntel U. Okonkwo", "Michela Traglia", "Cinzia Sala", "So-Youn Shin", "Corrado Masciullo", "Iwan Buetti", "Roberto Massacane", "Massimo Mangino", "Swee-Lay Thein", "Timothy D. Spector", "Santhi Ganesh", "Nicola Pirastu", "Paolo Gasparini", "Nicole Soranzo", "Clara Camaschella", "Daniel Hart", "Michael R. Green", "Daniela Toniolo"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0069206.s001", "https://dx.doi.org/10.1371/journal.pone.0069206.s002", "https://dx.doi.org/10.1371/journal.pone.0069206.s003", "https://dx.doi.org/10.1371/journal.pone.0069206.s004", "https://dx.doi.org/10.1371/journal.pone.0069206.s005", "https://dx.doi.org/10.1371/journal.pone.0069206.s006", "https://dx.doi.org/10.1371/journal.pone.0069206.s007"], "stats"=>{"downloads"=>48, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Genome_Wide_Association_Analysis_of_a_Founder_Population_Identified_TAF3_as_a_Gene_for_MCHC_in_Humans/761083", "title"=>"Genome Wide Association Analysis of a Founder Population Identified <i>TAF3</i> as a Gene for MCHC in Humans", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-07-31 02:36:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1138723"], "description"=>"<p>(A) Knockdown of <i>TAF3</i> by shRNA and its effect on <i>SPTA1</i> expression in human K562 cells, and in differentiating mouse MEL cells. 4 days after induction. Expression was monitored by qRT-PCR. NS: control scrambled shRNA; <i>TAF3</i>kd1 and <i>TAF3</i> kd2 and anti <i>Taf3</i> shRNAs described in Methods. (B) Chromatin immunoprecipitation analysis of the recruitment of <i>TAF3</i> and <i>TBP</i> to the indicated promoters in K562 cells shows that <i>TAF3</i> is associated with <i>SPTA1</i>. <i>TAF3</i>: ChIP with anti Taf3 Ab; IgG: control chromatin immunoprecipitation with IgG addition. Asterisks indicate a statistical significant difference (*  = <i>P</i><0.05; **  = <i>P</i><0.01) between control and TAF3 knockdown data for MEL and K562 cells, and between specific immunoprecipitations and IgG control immunoprecipitations.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "Genome-wide association studies", "Molecular cell biology", "Cellular structures", "cytoskeleton", "hematology", "anemia", "hematopoiesis", "Red cells", "transcriptionally", "regulated"], "article_id"=>761077, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Giorgio Pistis", "Shawntel U. Okonkwo", "Michela Traglia", "Cinzia Sala", "So-Youn Shin", "Corrado Masciullo", "Iwan Buetti", "Roberto Massacane", "Massimo Mangino", "Swee-Lay Thein", "Timothy D. Spector", "Santhi Ganesh", "Nicola Pirastu", "Paolo Gasparini", "Nicole Soranzo", "Clara Camaschella", "Daniel Hart", "Michael R. Green", "Daniela Toniolo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0069206.g002", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_SPTA1_gene_is_transcriptionally_regulated_by_TAF3_/761077", "title"=>"The <i>SPTA1</i> gene is transcriptionally regulated by <i>TAF3</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-31 02:36:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1138727"], "description"=>"<p>SNPs associated with MCHC in the INGI-VB cohort.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "Genome-wide association studies", "Molecular cell biology", "Cellular structures", "cytoskeleton", "hematology", "anemia", "hematopoiesis", "Red cells", "mchc", "ingi-vb"], "article_id"=>761081, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Giorgio Pistis", "Shawntel U. Okonkwo", "Michela Traglia", "Cinzia Sala", "So-Youn Shin", "Corrado Masciullo", "Iwan Buetti", "Roberto Massacane", "Massimo Mangino", "Swee-Lay Thein", "Timothy D. Spector", "Santhi Ganesh", "Nicola Pirastu", "Paolo Gasparini", "Nicole Soranzo", "Clara Camaschella", "Daniel Hart", "Michael R. Green", "Daniela Toniolo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0069206.t001", "stats"=>{"downloads"=>4, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_SNPs_associated_with_MCHC_in_the_INGI_VB_cohort_/761081", "title"=>"SNPs associated with MCHC in the INGI-VB cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-31 02:36:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1138725"], "description"=>"<p>rs1887582 association in general population cohorts.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "Genome-wide association studies", "Molecular cell biology", "Cellular structures", "cytoskeleton", "hematology", "anemia", "hematopoiesis", "Red cells"], "article_id"=>761079, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Giorgio Pistis", "Shawntel U. Okonkwo", "Michela Traglia", "Cinzia Sala", "So-Youn Shin", "Corrado Masciullo", "Iwan Buetti", "Roberto Massacane", "Massimo Mangino", "Swee-Lay Thein", "Timothy D. Spector", "Santhi Ganesh", "Nicola Pirastu", "Paolo Gasparini", "Nicole Soranzo", "Clara Camaschella", "Daniel Hart", "Michael R. Green", "Daniela Toniolo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0069206.t003", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rs1887582_association_in_general_population_cohorts_/761079", "title"=>"rs1887582 association in general population cohorts.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-31 02:36:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1138726"], "description"=>"*<p>Illegio-Sauris-Resia.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "Genome-wide association studies", "Molecular cell biology", "Cellular structures", "cytoskeleton", "hematology", "anemia", "hematopoiesis", "Red cells"], "article_id"=>761080, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Giorgio Pistis", "Shawntel U. Okonkwo", "Michela Traglia", "Cinzia Sala", "So-Youn Shin", "Corrado Masciullo", "Iwan Buetti", "Roberto Massacane", "Massimo Mangino", "Swee-Lay Thein", "Timothy D. Spector", "Santhi Ganesh", "Nicola Pirastu", "Paolo Gasparini", "Nicole Soranzo", "Clara Camaschella", "Daniel Hart", "Michael R. Green", "Daniela Toniolo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0069206.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rs1887582_replica_/761080", "title"=>"rs1887582 replica.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-31 02:36:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/1138721"], "description"=>"<p>(A) Association of genotyped and imputed SNPs. The top imputed SNP (rs11255458) is highlighted in violet, the other SNPs are colored according to their degree of linkage disequilibrium (r<sup>2</sup>) with rs11255458. The chromosomal positions (NCBI human genome Build 36) of the SNPs are plotted against genomic control-adjusted -log10 p-value. The estimated recombination rates (cM/Mb) from HapMap CEU release 22 are shown as gray lines. (B) The D'-based LD map was build using genotyped and imputed data of the INGI-VB population.</p>", "links"=>[], "tags"=>["genetics", "Human genetics", "Genetic association studies", "Genetics of disease", "Genome-wide association studies", "Molecular cell biology", "Cellular structures", "cytoskeleton", "hematology", "anemia", "hematopoiesis", "Red cells", "linkage", "disequilibrium", "taf3"], "article_id"=>761075, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Giorgio Pistis", "Shawntel U. Okonkwo", "Michela Traglia", "Cinzia Sala", "So-Youn Shin", "Corrado Masciullo", "Iwan Buetti", "Roberto Massacane", "Massimo Mangino", "Swee-Lay Thein", "Timothy D. Spector", "Santhi Ganesh", "Nicola Pirastu", "Paolo Gasparini", "Nicole Soranzo", "Clara Camaschella", "Daniel Hart", "Michael R. Green", "Daniela Toniolo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0069206.g001", "stats"=>{"downloads"=>3, "page_views"=>163, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Regional_association_plot_and_linkage_disequilibrium_pattern_at_the_TAF3_locus_/761075", "title"=>"Regional association plot and linkage disequilibrium pattern at the TAF3 locus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-31 02:36:01"}

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Relative Metric

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