Next-Generation Sequencing Identifies the Danforth's Short Tail Mouse Mutation as a Retrotransposon Insertion Affecting Ptf1a Expression
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{"title"=>"Next-Generation Sequencing Identifies the Danforth's Short Tail Mouse Mutation as a Retrotransposon Insertion Affecting Ptf1a Expression", "type"=>"journal", "authors"=>[{"first_name"=>"Christopher N.", "last_name"=>"Vlangos", "scopus_author_id"=>"6507299491"}, {"first_name"=>"Amanda N.", "last_name"=>"Siuniak", "scopus_author_id"=>"36495682900"}, {"first_name"=>"Dan", "last_name"=>"Robinson", "scopus_author_id"=>"7404645000"}, {"first_name"=>"Arul M.", "last_name"=>"Chinnaiyan", "scopus_author_id"=>"7006310597"}, {"first_name"=>"Robert H.", "last_name"=>"Lyons", "scopus_author_id"=>"8296775800"}, {"first_name"=>"James D.", "last_name"=>"Cavalcoli", "scopus_author_id"=>"35502953400"}, {"first_name"=>"Catherine E.", "last_name"=>"Keegan", "scopus_author_id"=>"7004829395"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84874768985", "doi"=>"10.1371/journal.pgen.1003205", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "issn"=>"15537390", "pmid"=>"23437000", "pui"=>"368490551", "sgr"=>"84874768985"}, "id"=>"51f14d55-a672-3c76-bbbb-bdf81e714922", "abstract"=>"The semidominant Danforth's short tail (Sd) mutation arose spontaneously in the 1920s. The homozygous Sd phenotype includes severe malformations of the axial skeleton with an absent tail, kidney agenesis, anal atresia, and persistent cloaca. The Sd mutant phenotype mirrors features seen in human caudal malformation syndromes including urorectal septum malformation, caudal regression, VACTERL association, and persistent cloaca. The Sd mutation was previously mapped to a 0.9 cM region on mouse chromosome 2qA3. We performed Sanger sequencing of exons and intron/exon boundaries mapping to the Sd critical region and did not identify any mutations. We then performed DNA enrichment/capture followed by next-generation sequencing (NGS) of the critical genomic region. Standard bioinformatic analysis of paired-end sequence data did not reveal any causative mutations. Interrogation of reads that had been discarded because only a single end mapped correctly to the Sd locus identified an early transposon (ETn) retroviral insertion at the Sd locus, located 12.5 kb upstream of the Ptf1a gene. We show that Ptf1a expression is significantly upregulated in Sd mutant embryos at E9.5. The identification of the Sd mutation will lead to improved understanding of the developmental pathways that are misregulated in human caudal malformation syndromes.", "link"=>"http://www.mendeley.com/research/nextgeneration-sequencing-identifies-danforths-short-tail-mouse-mutation-retrotransposon-insertion-a", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>9, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>9, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Hong Kong"=>1, "Brazil"=>2, "Germany"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/965606"], "description"=>"<p>Quantitative real time PCR plot of gene expression in RNA isolated from <i>Sd/Sd</i> (black bars), <i>Sd/</i>+ (hatched bars), and +/+ (grey bars) embryos of RefSeq genes mapping to the <i>Sd</i> interval. Y-axis shows fold change normalized to 1 for wildtype (+/+) expression. * denotes significance in expression levels where p<0.05 (For <i>Ptf1a</i>; <i>Sd</i>/+ versus +/+ p = 0.029, <i>Sd/Sd</i> versus +/+ p = 0.044).</p>", "links"=>[], "tags"=>["mutant"], "article_id"=>635328, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Christopher N. Vlangos", "Amanda N. Siuniak", "Dan Robinson", "Arul M. Chinnaiyan", "Robert H. Lyons Jr", "James D. Cavalcoli", "Catherine E. Keegan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003205.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gene_expression_at_E9_5_in_Sd_mutant_embryos_/635328", "title"=>"Gene expression at E9.5 in <i>Sd</i> mutant embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:21:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/1005113"], "description"=>"<p>Genes and ESTs mapping to the <i>Sd</i> critical region.</p>", "links"=>[], "tags"=>["ests"], "article_id"=>665734, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Christopher N. Vlangos", "Amanda N. Siuniak", "Dan Robinson", "Arul M. Chinnaiyan", "Robert H. Lyons Jr", "James D. Cavalcoli", "Catherine E. Keegan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003205.t001", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genes_and_ESTs_mapping_to_the_Sd_critical_region_/665734", "title"=>"Genes and ESTs mapping to the <i>Sd</i> critical region.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:35:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/965602"], "description"=>"<p><a href=\"http://www.genome.ucsc.edu\" target=\"_blank\">http://www.genome.ucsc.edu</a><b>).</b> The <i>Sd</i> region on chromosome 2 is defined by the flanking genetic markers D2Mit362 proximally and D2Mit364 distally (markers are highlighted in red) and represented by bases 18,686,882–20,915,358 on the July 2007 genome build (mm9). The <i>Sd</i> critical region contains 11 known genes. The mutation location is denoted by the red X.</p>", "links"=>[], "tags"=>["viewed", "ucsc", "genome", "browser"], "article_id"=>635324, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Christopher N. Vlangos", "Amanda N. Siuniak", "Dan Robinson", "Arul M. Chinnaiyan", "Robert H. Lyons Jr", "James D. Cavalcoli", "Catherine E. Keegan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003205.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Physical_map_of_the_Sd_critical_region_as_viewed_on_the_UCSC_genome_browser_/635324", "title"=>"Physical map of the <i>Sd</i> critical region as viewed on the UCSC genome browser (", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:20:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/965599"], "description"=>"<p>A) Heterozygous (<i>Sd</i>/+) mouse. B) Wildtype (+/+) mouse. C) Homozygous (<i>Sd/Sd</i>) P0 neonate. Note the lack of urogenital openings and tail. D) Wildtype (+/+) P0 neonate. E) Homozygous (<i>Sd/Sd</i>) mutant neonate showing bilateral kidney agenesis. Kidney location indicated by asterisks below the normally formed adrenal glands. F) Homozygous (<i>Sd/Sd</i>) mutant intestine. The colon ends blindly (indicated by arrow), never connecting to the rectum which is never formed (see panel C). The asterisk indicates normal formation of the caecum.</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "Computational biology", "developmental biology"], "article_id"=>635321, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Christopher N. Vlangos", "Amanda N. Siuniak", "Dan Robinson", "Arul M. Chinnaiyan", "Robert H. Lyons Jr", "James D. Cavalcoli", "Catherine E. Keegan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003205.g001", "stats"=>{"downloads"=>2, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Sd_phenotype_/635321", "title"=>"The <i>Sd</i> phenotype.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:19:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/965611", "https://ndownloader.figshare.com/files/965612", "https://ndownloader.figshare.com/files/965616", "https://ndownloader.figshare.com/files/965620"], "description"=>"<div><p>The semidominant Danforth's short tail (<i>Sd</i>) mutation arose spontaneously in the 1920s. The homozygous <i>Sd</i> phenotype includes severe malformations of the axial skeleton with an absent tail, kidney agenesis, anal atresia, and persistent cloaca. The <i>Sd</i> mutant phenotype mirrors features seen in human caudal malformation syndromes including urorectal septum malformation, caudal regression, VACTERL association, and persistent cloaca. The <i>Sd</i> mutation was previously mapped to a 0.9 cM region on mouse chromosome 2qA3. We performed Sanger sequencing of exons and intron/exon boundaries mapping to the <i>Sd</i> critical region and did not identify any mutations. We then performed DNA enrichment/capture followed by next-generation sequencing (NGS) of the critical genomic region. Standard bioinformatic analysis of paired-end sequence data did not reveal any causative mutations. Interrogation of reads that had been discarded because only a single end mapped correctly to the <i>Sd</i> locus identified an early transposon (ETn) retroviral insertion at the <i>Sd</i> locus, located 12.5 kb upstream of the <i>Ptf1a</i> gene. We show that <i>Ptf1a</i> expression is significantly upregulated in <i>Sd</i> mutant embryos at E9.5. The identification of the <i>Sd</i> mutation will lead to improved understanding of the developmental pathways that are misregulated in human caudal malformation syndromes.</p> </div>", "links"=>[], "tags"=>["next-generation", "sequencing", "identifies", "mutation", "retrotransposon", "insertion", "affecting", "expression"], "article_id"=>635332, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Christopher N. Vlangos", "Amanda N. Siuniak", "Dan Robinson", "Arul M. Chinnaiyan", "Robert H. Lyons Jr", "James D. Cavalcoli", "Catherine E. Keegan"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003205.s001", "https://dx.doi.org/10.1371/journal.pgen.1003205.s002", "https://dx.doi.org/10.1371/journal.pgen.1003205.s003", "https://dx.doi.org/10.1371/journal.pgen.1003205.s004"], "stats"=>{"downloads"=>19, "page_views"=>77, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Next_Generation_Sequencing_Identifies_the_Danforth_s_Short_Tail_Mouse_Mutation_as_a_Retrotransposon_Insertion_Affecting_Ptf1a_Expression__/635332", "title"=>"Next-Generation Sequencing Identifies the Danforth's Short Tail Mouse Mutation as a Retrotransposon Insertion Affecting <em>Ptf1a</em> Expression", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-02-22 11:21:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/965605"], "description"=>"<p>A) Southern analysis and PCR showing the presence of a large DNA insertion at the <i>Sd</i> locus. B) Multiplex PCR from inbred mouse lines showing the mutation is only present in <i>Sd</i> mice, and is not a polymorphism. In this three primer PCR reaction the <i>Sd</i> amplimer is 406 bp, while the WT amplimer is 510 bp. C) Mapping of the <i>Sd</i> mutation which we identified as an ETn (early transposon) in relation to nearby gene/ESTs, figure not to scale.</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "Computational biology", "developmental biology"], "article_id"=>635327, "categories"=>["Molecular Biology", "Biological Sciences", "Genetics", "Developmental Biology"], "users"=>["Christopher N. Vlangos", "Amanda N. Siuniak", "Dan Robinson", "Arul M. Chinnaiyan", "Robert H. Lyons Jr", "James D. Cavalcoli", "Catherine E. Keegan"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003205.g003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Confirmation_and_mapping_of_the_Sd_mutation_/635327", "title"=>"Confirmation and mapping of the <i>Sd</i> mutation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-22 11:20:54"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Computational biology", "average_usage"=>[295, 511, 651, 775, 882, 992, 1100, 1201, 1304, 1400, 1486, 1570, 1650]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[275, 472, 605, 720, 822, 921, 1013, 1106, 1200, 1289, 1378, 1459, 1531]}]}
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