Looking the Cow in the Eye: Deletion in the NID1 Gene Is Associated with Recessive Inherited Cataract in Romagnola Cattle
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{"title"=>"Looking the cow in the eye: Deletion in the NID1 gene is associated with recessive inherited cataract in romagnola cattle", "type"=>"journal", "authors"=>[{"first_name"=>"Leonardo", "last_name"=>"Murgiano", "scopus_author_id"=>"25633207200"}, {"first_name"=>"Vidhya", "last_name"=>"Jagannathan", "scopus_author_id"=>"7006778326"}, {"first_name"=>"Valerio", "last_name"=>"Calderoni", "scopus_author_id"=>"6504058523"}, {"first_name"=>"Monika", "last_name"=>"Joechler", "scopus_author_id"=>"55406771600"}, {"first_name"=>"Arcangelo", "last_name"=>"Gentile", "scopus_author_id"=>"7101970567"}, {"first_name"=>"Cord", "last_name"=>"Drögemüller", "scopus_author_id"=>"7005041360"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"600311354", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0110628", "scopus"=>"2-s2.0-84908568834", "pmid"=>"25347398", "sgr"=>"84908568834"}, "id"=>"b8172669-29df-3ae3-b959-b9e7e359449e", "abstract"=>"Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.", "link"=>"http://www.mendeley.com/research/looking-cow-eye-deletion-nid1-gene-associated-recessive-inherited-cataract-romagnola-cattle", "reader_count"=>16, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>2, "Veterinary Science and Veterinary Medicine"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Computer Science"=>2, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>2}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["http://files.figshare.com/1758036/Figure_1.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "users"=>["Valerio Calderoni", "Monika Joechler", "Arcangelo Gentile", "Cord Drögemüller", "Leonardo Murgiano", "Vidhya Jagannathan"], "links"=>[], "tags"=>["gene", "human", "missense point mutation", "matrix assembly complexes", "model", "exon", "NID 1 deletion", "crystal lens alterations", "monogenic autosomal recessive inheritance", "Romagnola Cattle Cataract", "Recessive Inherited Cataract", "NID 1 Gene", "cataract", "NID 1", "855 bp deletion", "locus"], "title"=>"<p>Cataract in Romagnola cattle.</p>", "figshare_url"=>"http://figshare.com/articles/_Cataract_in_Romagnola_cattle_/1218595", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0110628.g001"], "published_date"=>"2014-10-27 02:54:22", "article_id"=>1218595, "categories"=>["Biological Sciences"], "description"=>"<p>(<b>A</b>) Opacity of the left eye's noted from a distance. Case 3, born 27 July 2013, photo 4<sup>th</sup> November 2013. (<b>B</b>) Dioptric media opacity of the left eye. Case 2, born 16 <sup>th</sup> August 2013, photo 6 <sup>th</sup> November 2013. (<b>C</b>) Mild central nuclear opacity. Fundus only partially to view (yellow  =  tapetal retina; blue  =  papilla). Case 2, born 16 <sup>th</sup> August 2013, photo 6 <sup>th</sup> November 2013.</p>"}
  • {"files"=>["http://files.figshare.com/1758038/Figure_2.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "users"=>["Valerio Calderoni", "Monika Joechler", "Arcangelo Gentile", "Cord Drögemüller", "Leonardo Murgiano", "Vidhya Jagannathan"], "links"=>[], "tags"=>["gene", "human", "missense point mutation", "matrix assembly complexes", "model", "exon", "NID 1 deletion", "crystal lens alterations", "monogenic autosomal recessive inheritance", "Romagnola Cattle Cataract", "Recessive Inherited Cataract", "NID 1 Gene", "cataract", "NID 1", "855 bp deletion", "locus"], "title"=>"<p>Family tree showing four Romagnola calves affected by cataract and their parents.</p>", "figshare_url"=>"http://figshare.com/articles/_Family_tree_showing_four_Romagnola_calves_affected_by_cataract_and_their_parents_/1218597", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0110628.g002"], "published_date"=>"2014-10-27 02:54:22", "article_id"=>1218597, "categories"=>["Biological Sciences"], "description"=>"<p>Males are represented by squares, females by circles. Affected animals are shown with fully black symbols and genotyped carriers with a half-filled symbol. All unnamed animals with empty symbols were not available for genotyping. Note the inbreeding loop to the sire <i>Marte</i>.</p>"}
  • {"files"=>["http://files.figshare.com/1758044/Figure_3.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "users"=>["Valerio Calderoni", "Monika Joechler", "Arcangelo Gentile", "Cord Drögemüller", "Leonardo Murgiano", "Vidhya Jagannathan"], "links"=>[], "tags"=>["gene", "human", "missense point mutation", "matrix assembly complexes", "model", "exon", "NID 1 deletion", "crystal lens alterations", "monogenic autosomal recessive inheritance", "Romagnola Cattle Cataract", "Recessive Inherited Cataract", "NID 1 Gene", "cataract", "NID 1", "855 bp deletion", "locus"], "title"=>"<p>Mapping of the cataract mutation to BTA 28.</p>", "figshare_url"=>"http://figshare.com/articles/_Mapping_of_the_cataract_mutation_to_BTA_28_/1218603", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0110628.g003"], "published_date"=>"2014-10-27 02:54:22", "article_id"=>1218603, "categories"=>["Biological Sciences"], "description"=>"<p>(<b>A</b>) Results of the genome-wide association study (GWAS): Manhattan plot showing the negative log of the raw P values calculated with the mixed-model genotypic association test. Genome-wide significance thresholds are indicated (P≤0.01, solid red horizontal line at 7.7 10<sup>&#8722;8</sup> &#8211;log<sub>10</sub>Pvalue). (<b>B</b>) Detailed view of Manhattan plot for chromosome 28. (<b>C</b>) (blue) the 4 most significantly associated BTA 28 SNPs from GWAS in combination with the identical by descent (IBD; red) segments of the four affected animals. The names of the SNPs lines are reported along with their positions on the map.</p>"}
  • {"files"=>["http://files.figshare.com/1758998/Figure_S1.tif", "http://files.figshare.com/1758999/Figure_S2.tif", "http://files.figshare.com/1759000/Figure_S3.tif", "http://files.figshare.com/1759001/Figure_S4.pdf", "http://files.figshare.com/1759002/Table_S1.pdf", "http://files.figshare.com/1759003/Table_S2.pdf", "http://files.figshare.com/1759004/Table_S3.pdf", "http://files.figshare.com/1759005/Video_S1.mp4"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "users"=>["Valerio Calderoni", "Monika Joechler", "Arcangelo Gentile", "Cord Drögemüller", "Leonardo Murgiano", "Vidhya Jagannathan"], "links"=>[], "tags"=>["gene", "human", "missense point mutation", "matrix assembly complexes", "model", "exon", "NID 1 deletion", "crystal lens alterations", "monogenic autosomal recessive inheritance", "Romagnola Cattle Cataract", "Recessive Inherited Cataract", "NID 1 Gene", "cataract", "NID 1", "855 bp deletion", "locus"], "title"=>"Looking the Cow in the Eye: Deletion in the <i>NID1</i> Gene Is Associated with Recessive Inherited Cataract in Romagnola Cattle", "figshare_url"=>"http://figshare.com/articles/Looking_the_Cow_in_the_Eye_Deletion_in_the_NID1_Gene_Is_Associated_with_Recessive_Inherited_Cataract_in_Romagnola_Cattle/1219405", "defined_type"=>4, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0110628.s001", "http://dx.doi.org/10.1371/journal.pone.0110628.s002", "http://dx.doi.org/10.1371/journal.pone.0110628.s003", "http://dx.doi.org/10.1371/journal.pone.0110628.s004", "http://dx.doi.org/10.1371/journal.pone.0110628.s005", "http://dx.doi.org/10.1371/journal.pone.0110628.s006", "http://dx.doi.org/10.1371/journal.pone.0110628.s007", "http://dx.doi.org/10.1371/journal.pone.0110628.s008"], "published_date"=>"2014-10-27 15:25:07", "article_id"=>1219405, "categories"=>["Biological Sciences"], "description"=>"<div><p>Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (<i>NID1</i>) gene (c.3579_3604+829del). RT-PCR showed that <i>NID1</i> is expressed in bovine lenses while the transcript of the second locus was absent. The <i>NID1</i> deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. <i>Nidogen 1</i> deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds <i>NID1</i> to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.</p></div>"}
  • {"files"=>["http://files.figshare.com/1758048/Figure_4.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "users"=>["Valerio Calderoni", "Monika Joechler", "Arcangelo Gentile", "Cord Drögemüller", "Leonardo Murgiano", "Vidhya Jagannathan"], "links"=>[], "tags"=>["gene", "human", "missense point mutation", "matrix assembly complexes", "model", "exon", "NID 1 deletion", "crystal lens alterations", "monogenic autosomal recessive inheritance", "Romagnola Cattle Cataract", "Recessive Inherited Cataract", "NID 1 Gene", "cataract", "NID 1", "855 bp deletion", "locus"], "title"=>"<p>The <i>NID1</i> deletion.</p>", "figshare_url"=>"http://figshare.com/articles/_The_NID1_deletion_/1218607", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0110628.g004"], "published_date"=>"2014-10-27 02:54:22", "article_id"=>1218607, "categories"=>["Biological Sciences"], "description"=>"<p>(<b>A</b>) Gene content of the fine-mapped critical interval Position of the two extreme homozygous marker (red) from homozygosity mapping and of the nine most significant markers from GWAS (blue) are indicated. Annotated genes in the region are shown in black, along with <i>NID1</i> (green). (<b>B</b>) Screenshot of the next generation sequence reads mapped against the reference sequence. Note the 855 bp deletion. (<b>C</b>) Detected genotypes of the <i>NID1</i> deletion. Note the shorter PCR product in affected animals, the longer in controls and the presence of both products in carriers.</p>"}
  • {"files"=>["http://files.figshare.com/1758050/Figure_5.tif"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "users"=>["Valerio Calderoni", "Monika Joechler", "Arcangelo Gentile", "Cord Drögemüller", "Leonardo Murgiano", "Vidhya Jagannathan"], "links"=>[], "tags"=>["gene", "human", "missense point mutation", "matrix assembly complexes", "model", "exon", "NID 1 deletion", "crystal lens alterations", "monogenic autosomal recessive inheritance", "Romagnola Cattle Cataract", "Recessive Inherited Cataract", "NID 1 Gene", "cataract", "NID 1", "855 bp deletion", "locus"], "title"=>"<p>Tissue-specific inferred pathological mechanism.</p>", "figshare_url"=>"http://figshare.com/articles/_Tissue_specific_inferred_pathological_mechanism_/1218609", "defined_type"=>1, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0110628.g005"], "published_date"=>"2014-10-27 02:54:22", "article_id"=>1218609, "categories"=>["Biological Sciences"], "description"=>"<p>(<b>A</b>) Wild type transcript. The translated NID1 protein is shown. <i>S</i>: Signal peptide; <i>NIDO</i>: Nidogen domain; <i>E</i>: EGF-like domains <i>G2bb</i>: G2 beta-barrel domain; G3bp: G3 beta-propeller domain, binding laminin <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Takagi1\" target=\"_blank\">[36]</a> (<b>B</b>) Mutated NID1. The skipped exon is represented in red. The C-terminal part of the protein is altered severely and part of the G3 domain is lost. (<b>C</b>) Matrix assembly in various body tisses of an animal (like muscle, heart, kidney, skin, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Dong1\" target=\"_blank\">[31]</a>) with wild type NID; NID1 and NID2 are both expressed in detectable level; Both interact functionally with laminin and participate to the matrix assembly, probably compensating each for the lack of the other <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Yurchenco1\" target=\"_blank\">[41]</a>–<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Murshed1\" target=\"_blank\">[45]</a>. (<b>D</b>) Body tissues of an animal lacking a functional NID1: in all the tissue in which NID2 is expressed (all barring brain and lenses according to literature <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Dong1\" target=\"_blank\">[31]</a>) NID2 compensates for the lack of NID1 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Murshed1\" target=\"_blank\">[45]</a>–<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Miosge1\" target=\"_blank\">[47]</a>. (<b>E</b>) Eye of an individual with functional NID1. NID2 is not expressed at detectable levels, but NID1 alone is enough in its role of bridge protein in the matrix assembly. (<b>F</b>) Eye of an individual lacking of functional NID1. NID1 cannot interact functionally with laminin, and this defect is not compensated in the lens tissue, leading to matrix instability and ultimately to a pathological condition. (<b>C-F</b>) Simplified version of basal membrane <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Timpl1\" target=\"_blank\">[38]</a>. <i>NID1</i>: Nidogen 1. <i>NID2</i>: Nidogen 2. <i>Lam</i>: Laminins. <i>Col IV</i>: Collagen IV. <i>Perl</i>: Perlecan. Only interactions of the Nidogens with other elements are shown. Nidogens role is to bridge the interactions among the main matrix proteins <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110628#pone.0110628-Takagi1\" target=\"_blank\">[36]</a>.</p>"}
  • {"files"=>["http://files.figshare.com/1758051/None.xls"], "pos_in_sequence"=>0, "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "users"=>["Valerio Calderoni", "Monika Joechler", "Arcangelo Gentile", "Cord Drögemüller", "Leonardo Murgiano", "Vidhya Jagannathan"], "links"=>[], "tags"=>["gene", "human", "missense point mutation", "matrix assembly complexes", "model", "exon", "NID 1 deletion", "crystal lens alterations", "monogenic autosomal recessive inheritance", "Romagnola Cattle Cataract", "Recessive Inherited Cataract", "NID 1 Gene", "cataract", "NID 1", "855 bp deletion", "locus"], "title"=>"<p><b>Table 1.</b> Association of coding variants with the cataract phenotype in Romagnola cattle.</p>", "figshare_url"=>"http://figshare.com/articles/_Table_1_Association_of_coding_variants_with_the_cataract_phenotype_in_Romagnola_cattle_/1218610", "defined_type"=>3, "doi"=>["http://dx.doi.org/10.1371/journal.pone.0110628.t001"], "published_date"=>"2014-10-27 02:54:22", "article_id"=>1218610, "categories"=>["Biological Sciences"], "description"=>"<p><b>Table 1.</b> Association of coding variants with the cataract phenotype in Romagnola cattle.</p>"}

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Relative Metric

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