Fine Mapping for Weaver Syndrome in Brown Swiss Cattle and the Identification of 41 Concordant Mutations across NRCAM, PNPLA8 and CTTNBP2
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{"title"=>"Fine Mapping for Weaver Syndrome in Brown Swiss Cattle and the Identification of 41 Concordant Mutations across NRCAM, PNPLA8 and CTTNBP2", "type"=>"journal", "authors"=>[{"first_name"=>"Matthew", "last_name"=>"McClure", "scopus_author_id"=>"35503410100"}, {"first_name"=>"Euisoo", "last_name"=>"Kim", "scopus_author_id"=>"26424677500"}, {"first_name"=>"Derek", "last_name"=>"Bickhart", "scopus_author_id"=>"15756929400"}, {"first_name"=>"Daniel", "last_name"=>"Null", "scopus_author_id"=>"26531450800"}, {"first_name"=>"Tabatha", "last_name"=>"Cooper", "scopus_author_id"=>"18334272100"}, {"first_name"=>"John", "last_name"=>"Cole", "scopus_author_id"=>"7403376306"}, {"first_name"=>"George", "last_name"=>"Wiggans", "scopus_author_id"=>"7005272094"}, {"first_name"=>"Paolo", "last_name"=>"Ajmone-Marsan", "scopus_author_id"=>"6701754363"}, {"first_name"=>"Licia", "last_name"=>"Colli", "scopus_author_id"=>"24757901400"}, {"first_name"=>"Enrico", "last_name"=>"Santus", "scopus_author_id"=>"12808342500"}, {"first_name"=>"George E.", "last_name"=>"Liu", "scopus_author_id"=>"14054315600"}, {"first_name"=>"Steve", "last_name"=>"Schroeder", "scopus_author_id"=>"18936964800"}, {"first_name"=>"Lakshmi", "last_name"=>"Matukumalli", "scopus_author_id"=>"6508165049"}, {"first_name"=>"Curt", "last_name"=>"Van Tassell", "scopus_author_id"=>"23394469300"}, {"first_name"=>"Tad", "last_name"=>"Sonstegard", "scopus_author_id"=>"7003447943"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23527149", "sgr"=>"84875195766", "doi"=>"10.1371/journal.pone.0059251", "scopus"=>"2-s2.0-84875195766", "pui"=>"368562459", "issn"=>"19326203"}, "id"=>"61fb46f6-48e9-3206-8dfd-22c5e83d21bd", "abstract"=>"Bovine Progressive Degenerative Myeloencephalopathy (Weaver Syndrome) is a recessive neurological disease that has been observed in the Brown Swiss cattle breed since the 1970's in North America and Europe. Bilateral hind leg weakness and ataxia appear in afflicted animals at 6 to 18 months of age, and slowly progresses to total loss of hind limb control by 3 to 4 years of age. While Weaver has previously been mapped to Bos taurus autosome (BTA) 4∶46-56 Mb and a diagnostic test based on the 6 microsatellite (MS) markers is commercially available, neither the causative gene nor mutation has been identified; therefore misdiagnosis can occur due to recombination between the diagnostic MS markers and the causative mutation. Analysis of 34,980 BTA 4 SNPs genotypes derived from the Illumina BovineHD assay for 20 Brown Swiss Weaver carriers and 49 homozygous normal bulls refined the Weaver locus to 48-53 Mb. Genotyping of 153 SNPs, identified from whole genome sequencing of 10 normal and 10 carrier animals, across a validation set of 841 animals resulted in the identification of 41 diagnostic SNPs that were concordant with the disease. Except for one intergenic SNP all are associated with genes expressed in nervous tissues: 37 distal to NRCAM, one non-synonymous (serine to asparagine) in PNPLA8, one synonymous and one non-synonymous (lysine to glutamic acid) in CTTNBP2. Haplotype and imputation analyses of 7,458 Brown Swiss animals with Illumina BovineSNP50 data and the 41 diagnostic SNPs resulted in the identification of only one haplotype concordant with the Weaver phenotype. Use of this haplotype and the diagnostic SNPs more accurately identifies Weaver carriers in both Brown Swiss purebred and influenced herds.", "link"=>"http://www.mendeley.com/research/fine-mapping-weaver-syndrome-brown-swiss-cattle-identification-41-concordant-mutations-across-nrcam", "reader_count"=>14, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>1, "Other"=>1, "Student > Master"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>13, "Medicine and Dentistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}}, "reader_count_by_country"=>{"Colombia"=>1, "United States"=>1, "United Kingdom"=>1, "France"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1007807"], "description"=>"a<p>The homozyous allele in affected animals.</p>b<p>Affected predicted TFBS information in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059251#pone-0059251-t003\" target=\"_blank\">Table 3.</a></p>c<p>Bovine EST: AJ677346.</p>d<p>None of the listed dbSNP IDs are validated.</p>e<p>mRNA (n = 56) at SNP 49656945, partial list: JO339806, JU559277, JV452054, AK382080, BC024441, AK231430.</p>f<p>mRNA (N = 4) at SNP 49706022: JO339806, JO397144, AK382080, JO62179.</p>g<p>SNP is heterozygous in one Holstein bull with 4% non Holstein genomic influence.</p>", "links"=>[], "tags"=>["snp", "interactions"], "article_id"=>668419, "categories"=>["Biotechnology", "Genetics"], "users"=>["Matthew McClure", "Euisoo Kim", "Derek Bickhart", "Daniel Null", "Tabatha Cooper", "John Cole", "George Wiggans", "Paolo Ajmone-Marsan", "Licia Colli", "Enrico Santus", "George E. Liu", "Steve Schroeder", "Lakshmi Matukumalli", "Curt Van Tassell", "Tad Sonstegard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059251.t001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Target_SNP_interactions_and_filter_information_/668419", "title"=>"Target SNP interactions and filter information.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-20 02:20:19"}
  • {"files"=>["https://ndownloader.figshare.com/files/992911"], "description"=>"<p>GWAS results using reported Weaver phenotypes for 72 individuals with HDSNP genotypes for <b>A</b>) all BTAs <b>B</b>) BTA 4. <b>C</b>) GWAS results for BTA 4 using reported Weaver phenotypes for 829 individuals with target, 50K, and/or HD genotypes. UMD3.1 coordinates used.</p>", "links"=>[], "tags"=>["genetics and genomics", "biotechnology"], "article_id"=>656501, "categories"=>["Biotechnology", "Genetics"], "users"=>["Matthew McClure", "Euisoo Kim", "Derek Bickhart", "Daniel Null", "Tabatha Cooper", "John Cole", "George Wiggans", "Paolo Ajmone-Marsan", "Licia Colli", "Enrico Santus", "George E. Liu", "Steve Schroeder", "Lakshmi Matukumalli", "Curt Van Tassell", "Tad Sonstegard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059251.g001", "stats"=>{"downloads"=>5, "page_views"=>49, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Weaver_Syndrome_GWAS_/656501", "title"=>"Weaver Syndrome GWAS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-21 03:48:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/992913"], "description"=>"<p>Graph created using data from <a href=\"http://www.biogps.org\" target=\"_blank\">www.biogps.org</a> (accessed 7/18/2012) for mRNA expression levels of the gene’s mRNA expression across 84 mouse and humans tissues. While few gene expression across multiple tissues have been done in bovine, it is logical to expect a similar expression pattern as shown above given the high gene exon homology of PNPLA8, CTTNBP2, and NRCAM between bovine, mouse, human, and other mammalian species (ENSEMBL).</p>", "links"=>[], "tags"=>["genetics and genomics", "biotechnology"], "article_id"=>656502, "categories"=>["Biotechnology", "Genetics"], "users"=>["Matthew McClure", "Euisoo Kim", "Derek Bickhart", "Daniel Null", "Tabatha Cooper", "John Cole", "George Wiggans", "Paolo Ajmone-Marsan", "Licia Colli", "Enrico Santus", "George E. Liu", "Steve Schroeder", "Lakshmi Matukumalli", "Curt Van Tassell", "Tad Sonstegard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059251.g002", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mRNA_expression_levels_of_NRCAM_PNPLA8_CTTNBP2_/656502", "title"=>"mRNA expression levels of NRCAM, PNPLA8, CTTNBP2.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-21 03:49:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/992916"], "description"=>"<p>Bottom portion of the figure highlights the annotated human exons (brown cross hatch) for NRCAM which align to an unannotated portion of the bovine genome. UMD3.1 assembly used.</p>", "links"=>[], "tags"=>["alignment", "bovine", "annotations", "nrcam"], "article_id"=>656503, "categories"=>["Biotechnology", "Genetics"], "users"=>["Matthew McClure", "Euisoo Kim", "Derek Bickhart", "Daniel Null", "Tabatha Cooper", "John Cole", "George Wiggans", "Paolo Ajmone-Marsan", "Licia Colli", "Enrico Santus", "George E. Liu", "Steve Schroeder", "Lakshmi Matukumalli", "Curt Van Tassell", "Tad Sonstegard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059251.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ensembl_alignment_of_the_bovine_and_human_annotations_from_NRCAM_to_PNPLA8_/656503", "title"=>"Ensembl alignment of the bovine and human annotations from NRCAM to PNPLA8.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-21 03:50:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/992917", "https://ndownloader.figshare.com/files/992918", "https://ndownloader.figshare.com/files/992919", "https://ndownloader.figshare.com/files/992921", "https://ndownloader.figshare.com/files/992922"], "description"=>"<div><p>Bovine Progressive Degenerative Myeloencephalopathy (Weaver Syndrome) is a recessive neurological disease that has been observed in the Brown Swiss cattle breed since the 1970’s in North America and Europe. Bilateral hind leg weakness and ataxia appear in afflicted animals at 6 to 18 months of age, and slowly progresses to total loss of hind limb control by 3 to 4 years of age. While Weaver has previously been mapped to <i>Bos taurus</i> autosome (BTA) 4∶46–56 Mb and a diagnostic test based on the 6 microsatellite (MS) markers is commercially available, neither the causative gene nor mutation has been identified; therefore misdiagnosis can occur due to recombination between the diagnostic MS markers and the causative mutation. Analysis of 34,980 BTA 4 SNPs genotypes derived from the Illumina BovineHD assay for 20 Brown Swiss Weaver carriers and 49 homozygous normal bulls refined the Weaver locus to 48–53 Mb. Genotyping of 153 SNPs, identified from whole genome sequencing of 10 normal and 10 carrier animals, across a validation set of 841 animals resulted in the identification of 41 diagnostic SNPs that were concordant with the disease. Except for one intergenic SNP all are associated with genes expressed in nervous tissues: 37 distal to <i>NRCAM</i>, one non-synonymous (serine to asparagine) in <i>PNPLA8,</i> one synonymous and one non-synonymous (lysine to glutamic acid) in <i>CTTNBP2</i>. Haplotype and imputation analyses of 7,458 Brown Swiss animals with Illumina BovineSNP50 data and the 41 diagnostic SNPs resulted in the identification of only one haplotype concordant with the Weaver phenotype. Use of this haplotype and the diagnostic SNPs more accurately identifies Weaver carriers in both Brown Swiss purebred and influenced herds.</p> </div>", "links"=>[], "tags"=>["weaver", "swiss", "41", "concordant", "mutations", "pnpla8", "cttnbp2"], "article_id"=>656504, "categories"=>["Biotechnology", "Genetics"], "users"=>["Matthew McClure", "Euisoo Kim", "Derek Bickhart", "Daniel Null", "Tabatha Cooper", "John Cole", "George Wiggans", "Paolo Ajmone-Marsan", "Licia Colli", "Enrico Santus", "George E. Liu", "Steve Schroeder", "Lakshmi Matukumalli", "Curt Van Tassell", "Tad Sonstegard"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059251.s001", "https://dx.doi.org/10.1371/journal.pone.0059251.s002", "https://dx.doi.org/10.1371/journal.pone.0059251.s003", "https://dx.doi.org/10.1371/journal.pone.0059251.s004", "https://dx.doi.org/10.1371/journal.pone.0059251.s005"], "stats"=>{"downloads"=>20, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Fine_Mapping_for_Weaver_Syndrome_in_Brown_Swiss_Cattle_and_the_Identification_of_41_Concordant_Mutations_across_NRCAM_PNPLA8_and_CTTNBP2__/656504", "title"=>"Fine Mapping for Weaver Syndrome in Brown Swiss Cattle and the Identification of 41 Concordant Mutations across NRCAM, PNPLA8 and CTTNBP2", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-21 03:50:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1007776"], "description"=>"a<p>Associations predicted by STRING (Jensen et al. 2009).</p>b<p>Count of association steps between genes.</p>", "links"=>[], "tags"=>["associations", "genes", "weaver", "locus", "familial"], "article_id"=>668393, "categories"=>["Biotechnology", "Genetics"], "users"=>["Matthew McClure", "Euisoo Kim", "Derek Bickhart", "Daniel Null", "Tabatha Cooper", "John Cole", "George Wiggans", "Paolo Ajmone-Marsan", "Licia Colli", "Enrico Santus", "George E. Liu", "Steve Schroeder", "Lakshmi Matukumalli", "Curt Van Tassell", "Tad Sonstegard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059251.t003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_associations_between_genes_in_Weaver_locus_and_familial_ALS_/668393", "title"=>"Predicted associations between genes in Weaver locus and familial ALS.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-20 02:19:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1007751"], "description"=>"a<p>UMD3.1, chromosome 4 positions.</p>b<p>Comparision of TFBS for reference and alternative base pair.</p>c<p>Predicted TFBS’s PSSM similarity value was below the threshold and was not called for this allele. Often this is due to a change in the consensus binding site of the TFBS by the polymorphic base of the SNP.</p>", "links"=>[], "tags"=>["tfbs", "affected", "targeted", "weaver"], "article_id"=>668367, "categories"=>["Biotechnology", "Genetics"], "users"=>["Matthew McClure", "Euisoo Kim", "Derek Bickhart", "Daniel Null", "Tabatha Cooper", "John Cole", "George Wiggans", "Paolo Ajmone-Marsan", "Licia Colli", "Enrico Santus", "George E. Liu", "Steve Schroeder", "Lakshmi Matukumalli", "Curt Van Tassell", "Tad Sonstegard"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0059251.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Predicted_TFBS_that_are_affected_by_targeted_Weaver_SNP_/668367", "title"=>"Predicted TFBS that are affected by targeted Weaver SNP.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-20 02:19:27"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
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  • {"unique-ip"=>"13", "full-text"=>"7", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"15", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"12", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
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  • {"unique-ip"=>"24", "full-text"=>"17", "pdf"=>"10", "abstract"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"19", "full-text"=>"19", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"4", "abstract"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
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  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
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  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
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  • {"unique-ip"=>"20", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"10", "cited-by"=>"0", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"10", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"14", "full-text"=>"42", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"11"}
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  • {"unique-ip"=>"14", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
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  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"11", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
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Relative Metric

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