Shared Segment Analysis and Next-Generation Sequencing Implicates the Retinoic Acid Signaling Pathway in Total Anomalous Pulmonary Venous Return (TAPVR)
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{"title"=>"Shared segment analysis and next-generation sequencing implicates the retinoic acid signaling pathway in Total Anomalous Pulmonary Venous Return (TAPVR)", "type"=>"journal", "authors"=>[{"first_name"=>"Dustin", "last_name"=>"Nash", "scopus_author_id"=>"56765254500"}, {"first_name"=>"Cammon B.", "last_name"=>"Arrington", "scopus_author_id"=>"9744158200"}, {"first_name"=>"Brett J.", "last_name"=>"Kennedy", "scopus_author_id"=>"56117024900"}, {"first_name"=>"Mark", "last_name"=>"Yandell", "scopus_author_id"=>"6601908759"}, {"first_name"=>"Wilfred", "last_name"=>"Wu", "scopus_author_id"=>"55881654500"}, {"first_name"=>"Wenying", "last_name"=>"Zhang", "scopus_author_id"=>"55800047500"}, {"first_name"=>"Stephanie", "last_name"=>"Ware", "scopus_author_id"=>"7005126505"}, {"first_name"=>"Lynn B.", "last_name"=>"Jorde", "scopus_author_id"=>"7005967858"}, {"first_name"=>"Peter J.", "last_name"=>"Gruber", "scopus_author_id"=>"7006614042"}, {"first_name"=>"H. Joseph", "last_name"=>"Yost", "scopus_author_id"=>"7005557097"}, {"first_name"=>"Neil E.", "last_name"=>"Bowles", "scopus_author_id"=>"7005278993"}, {"first_name"=>"Steven B.", "last_name"=>"Bleyl", "scopus_author_id"=>"6507620798"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84938702835", "pui"=>"605481206", "doi"=>"10.1371/journal.pone.0131514", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84938702835", "pmid"=>"26121141"}, "id"=>"e966642f-61d8-3a43-8a2a-cce998d1b25e", "abstract"=>"Most isolated congenital heart defects are thought to be sporadic and are often ascribed to multifactorial mechanisms with poorly understood genetics. Total Anomalous Pulmonary Venous Return (TAPVR) occurs in 1 in 15,000 live-born infants and occurs either in isolation or as part of a syndrome involving aberrant left-right development. Previously, we reported causative links between TAVPR and the PDGFRA gene. TAPVR has also been linked to the ANKRD1/CARP genes. However, these genes only explain a small fraction of the heritability of the condition. By examination of phased single nucleotide polymorphism genotype data from 5 distantly related TAPVR patients we identified a single 25 cM shared, Identical by Descent genomic segment on the short arm of chromosome 12 shared by 3 of the patients and their obligate-carrier parents. Whole genome sequence (WGS) analysis identified a non-synonymous variant within the shared segment in the retinol binding protein 5 (RBP5) gene. The RBP5 variant is predicted to be deleterious and is overrepresented in the TAPVR population. Gene expression and functional analysis of the zebrafish orthologue, rbp7, supports the notion that RBP5 is a TAPVR susceptibility gene. Additional sequence analysis also uncovered deleterious variants in genes associated with retinoic acid signaling, including NODAL and retinol dehydrogenase 10. These data indicate that genetic variation in the retinoic acid signaling pathway confers, in part, susceptibility to TAPVR.", "link"=>"http://www.mendeley.com/research/shared-segment-analysis-nextgeneration-sequencing-implicates-retinoic-acid-signaling-pathway-total-a", "reader_count"=>9, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Mathematics"=>1, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Sports and Recreations"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2153928"], "description"=>"<p>Two pedigrees with TAPVR affected patients which shared genomic segments greater than 5cM. The colors below the patient ID correspond with the IBD segments shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131514#pone.0131514.g002\" target=\"_blank\">Fig 2</a>. Note, the affected siblings 2012 and 2013 are related to other TAPVR affected individuals through two separate lineages (both through their mother) as depicted by two pedigrees.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466977, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_Shared_Genomic_Segments_in_TAPVR_pedigrees_/1466977", "title"=>"Identification of Shared Genomic Segments in TAPVR pedigrees.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153930"], "description"=>"<p>The different colors on the inside of each circle show the patients which shared the IBD segment at each of the positions (based in the color code in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131514#pone.0131514.g001\" target=\"_blank\">Fig 1</a>).</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466979, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Representation_of_the_IBD_segments_gt_5cM_that_were_shared_by_2_or_more_TAPVR_patients_or_their_parents_/1466979", "title"=>"Representation of the IBD segments >5cM that were shared by 2 or more TAPVR patients or their parents.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153934"], "description"=>"<p><i>rbp7a</i> is strongly expressed within the dorsal forerunner cells (DFCs) and Kupffer’s vesicle (KV) in the developing zebrafish embryo: Panel A. 75% epiboly; Panel B. tailbud stage; Panel C. 8 somite stage.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466983, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g003", "stats"=>{"downloads"=>6, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rbp7a_expression_in_the_developing_Zebrafish_/1466983", "title"=>"<i>rbp7a</i> expression in the developing Zebrafish.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153935"], "description"=>"<p>Morpholino knockdown of rbp7a results in randomized heart looping. <i>cmlc2</i> expression at 38 hpf is used to visualize heart looping. Panel A: normal, left-sided heart looping; Panel B: reversed, right-sided heart looping; Panel C: Reversed heart looping occurs in 2% of uninjected control (WT) embryos (n = 315) and 42% of <i>rbp7a</i> morphant (MO) embryos (n = 312).</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466984, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g004", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_rbp7a_knockdown_on_zebrafish_heart_looping_/1466984", "title"=>"Effects of rbp7a knockdown on zebrafish heart looping.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153936"], "description"=>"<p>Panel A: representative images showing, left-sided <i>spaw</i> expression, right sided <i>spaw</i> expression, bilateral <i>spaw</i> expression and no <i>spaw</i> expression. Panel B. <i>spaw</i> scoring in WT (blue bars) and <i>rbp7a</i> morphant (MO) embryos (purple bars).</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466985, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g005", "stats"=>{"downloads"=>3, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Morpholino_knockdown_of_rbp7a_results_in_perturbed_spaw_expression_/1466985", "title"=>"Morpholino knockdown of rbp7a results in perturbed <i>spaw</i> expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153937"], "description"=>"<p>Panels A and B: Immunohistochemical staining of representative WT and morphant KV and cilia. Panel C: <i>rbp7a</i> morphants have shorter but not fewer KV cilia than WT embryos. * p<0.05.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466986, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g006", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_KV_cilia_are_shortened_in_rbp7a_morphants_/1466986", "title"=>"KV cilia are shortened in <i>rbp7a</i> morphants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153938"], "description"=>"<p>Panel A: Injection of <i>rbp7a</i> (blue bars) or <i>spaw</i> (purple bars) morpholinos at standard concentrations results in significantly altered <i>spaw</i> expression. Panel B: Injection of either morpholino at subthreshold doses (<i>rbp7a</i>: blue bars; <i>spaw</i>: purple bars) results in more normal left-sided <i>spaw</i> expression. However, co-injection of both morpholinos at subthreshold doses leads to significantly altered <i>spaw</i> expression, similar to the higher dose <i>spaw</i> morphants.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466987, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g007", "stats"=>{"downloads"=>3, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_rbp7a_and_spaw_function_together_in_left_right_development_/1466987", "title"=>"<i>rbp7a</i> and <i>spaw</i> function together in left-right development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153939"], "description"=>"<p>The Rbp5 variant is inherited from a common ancestor whereas the “second genetic hits” (the Nodal and Rdh10 variants) are inherited from the other parent. Note DNA was not available for the father of patients 2012 and 2103. However, the NODAL variant was not detected in DNA isolated from the peripheral blood of their mother suggesting it was inherited from their father.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466988, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.g008", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_of_digenic_inheritence_for_TAPVR_/1466988", "title"=>"Model of digenic inheritence for TAPVR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153940"], "description"=>"<p>VAAST Analysis of the WGS variants identified in the chromosome 12 SGS.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466989, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.t001", "stats"=>{"downloads"=>7, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_VAAST_Analysis_of_the_WGS_variants_identified_in_the_chromosome_12_SGS_/1466989", "title"=>"VAAST Analysis of the WGS variants identified in the chromosome 12 SGS.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153946"], "description"=>"<p>Variants in the chromosome 12 SGS predicted damaging/deleterious by MutationTaster/Polyphen2 and SIFT.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466991, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.t002", "stats"=>{"downloads"=>2, "page_views"=>26, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Variants_in_the_chromosome_12_SGS_predicted_damaging_deleterious_by_MutationTaster_Polyphen2_and_SIFT_/1466991", "title"=>"Variants in the chromosome 12 SGS predicted damaging/deleterious by MutationTaster/Polyphen2 and SIFT.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153956"], "description"=>"<p>Comparison of the allelic frequency of rs7969705 in 64 TAPVR cases and 149 heterotaxy cases versus non-Finnish Europeans in the ExAC database.</p>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466992, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0131514.t003", "stats"=>{"downloads"=>6, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_the_allelic_frequency_of_rs7969705_in_64_TAPVR_cases_and_149_heterotaxy_cases_versus_non_Finnish_Europeans_in_the_ExAC_database_/1466992", "title"=>"Comparison of the allelic frequency of rs7969705 in 64 TAPVR cases and 149 heterotaxy cases versus non-Finnish Europeans in the ExAC database.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-06-29 02:47:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/2153957", "https://ndownloader.figshare.com/files/2153958", "https://ndownloader.figshare.com/files/2153959"], "description"=>"<div><p>Most isolated congenital heart defects are thought to be sporadic and are often ascribed to multifactorial mechanisms with poorly understood genetics. Total Anomalous Pulmonary Venous Return (TAPVR) occurs in 1 in 15,000 live-born infants and occurs either in isolation or as part of a syndrome involving aberrant left-right development. Previously, we reported causative links between TAVPR and the <i>PDGFRA</i> gene. TAPVR has also been linked to the <i>ANKRD1/CARP</i> genes. However, these genes only explain a small fraction of the heritability of the condition. By examination of phased single nucleotide polymorphism genotype data from 5 distantly related TAPVR patients we identified a single 25 cM shared, Identical by Descent genomic segment on the short arm of chromosome 12 shared by 3 of the patients and their obligate-carrier parents. Whole genome sequence (WGS) analysis identified a non-synonymous variant within the shared segment in the <i>retinol binding protein 5</i> (<i>RBP5</i>) gene. The <i>RBP5</i> variant is predicted to be deleterious and is overrepresented in the TAPVR population. Gene expression and functional analysis of the zebrafish orthologue, <i>rbp7</i>, supports the notion that <i>RBP5</i> is a TAPVR susceptibility gene. Additional sequence analysis also uncovered deleterious variants in genes associated with retinoic acid signaling, including <i>NODAL</i> and <i>retinol dehydrogenase 10</i>. These data indicate that genetic variation in the retinoic acid signaling pathway confers, in part, susceptibility to TAPVR.</p></div>", "links"=>[], "tags"=>["ANKRD", "Descent genomic segment", "Retinoic acid", "nucleotide polymorphism genotype data", "wgs", "TAPVR susceptibility gene", "Additional sequence analysis", "RBP 5 variant", "pdgfra", "nodal", "Total Anomalous Pulmonary Venous Return", "retinol dehydrogenase 10.", "Whole Genome Sequence", "retinol binding protein 5", "TAVPR", "Shared Segment Analysis"], "article_id"=>1466993, "categories"=>["Uncategorised"], "users"=>["Dustin Nash", "Cammon B. Arrington", "Brett J. Kennedy", "Mark Yandell", "Wilfred Wu", "Wenying Zhang", "Stephanie Ware", "Lynn B. Jorde", "Peter J. Gruber", "H. Joseph Yost", "Neil E. Bowles", "Steven B. Bleyl"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0131514.s001", "https://dx.doi.org/10.1371/journal.pone.0131514.s002", "https://dx.doi.org/10.1371/journal.pone.0131514.s003"], "stats"=>{"downloads"=>5, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Shared_Segment_Analysis_and_Next_Generation_Sequencing_Implicates_the_Retinoic_Acid_Signaling_Pathway_in_Total_Anomalous_Pulmonary_Venous_Return_TAPVR_/1466993", "title"=>"Shared Segment Analysis and Next-Generation Sequencing Implicates the Retinoic Acid Signaling Pathway in Total Anomalous Pulmonary Venous Return (TAPVR)", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-06-29 02:47:15"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"15", "full-text"=>"17", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"7", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}

Relative Metric

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