A Novel Missense Mutation in ADAMTS10 in Norwegian Elkhound Primary Glaucoma
Publication Date
November 05, 2014
Journal
PLOS ONE
Authors
Saija J. Ahonen, Maria Kaukonen, Forrest D. Nussdorfer, Christine D. Harman, et al
Volume
9
Issue
11
Pages
e111941
DOI
https://dx.plos.org/10.1371/journal.pone.0111941
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0111941
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/25372548
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221187
Europe PMC
http://europepmc.org/abstract/MED/25372548
Web of Science
000344556900093
Scopus
84910598703
Mendeley
http://www.mendeley.com/research/novel-missense-mutation-adamts10-norwegian-elkhound-primary-glaucoma
Events
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1780385"], "description"=>"<p><b>A</b>) A Manhattan plot of genome-wide case-control association analysis with 8 cases and 9 controls indicate the most highly associated region in CFA20. <b>B</b>) The glaucoma associated region on chromosome 20 spans from 53.1 Mb to 53.8 Mb. <b>C</b>) Genotypes at the associated region on CFA20. All cases share a 750 kb homozygous block. <b>D</b>) The associated region harbors 35 genes of which only <i>ADAMTS10</i> has been associated with POAG.</p>", "links"=>[], "tags"=>["poag", "pcg", "Norwegian Elkhound", "mutation", "uk", "ADAMTS 10 biology", "387T", "ne", "glaucoma", "PCAG", "750 kb region", "novel missense mutation", "glaucoma gene"], "article_id"=>1229869, "categories"=>["Biological Sciences"], "users"=>["Saija J. Ahonen", "Maria Kaukonen", "Forrest D. Nussdorfer", "Christine D. Harman", "András M. Komáromy", "Hannes Lohi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111941.g002", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genome_wide_association_study_/1229869", "title"=>"Genome wide association study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-05 04:18:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780386"], "description"=>"<p><b>A</b>) A schematic representation of the <i>ADAMTS10</i> gene structure. The gene is composed of 24 coding exons (dark blue) and the c.1441G>A variant is positioned in the exon 9 (not in scale). <b>B</b>) Chromatograms of the non-synonymous variant position in an affected, a carrier and a wild-type dog. <b>C</b>) The p.A387T variant is positioned in the catalytic metalloprotease domain.</p>", "links"=>[], "tags"=>["poag", "pcg", "Norwegian Elkhound", "mutation", "uk", "ADAMTS 10 biology", "387T", "ne", "glaucoma", "PCAG", "750 kb region", "novel missense mutation", "glaucoma gene"], "article_id"=>1229870, "categories"=>["Biological Sciences"], "users"=>["Saija J. Ahonen", "Maria Kaukonen", "Forrest D. Nussdorfer", "Christine D. Harman", "András M. Komáromy", "Hannes Lohi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111941.g003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_missense_mutation_in_the_ADAMTS10_/1229870", "title"=>"A missense mutation in the <i>ADAMTS10</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-05 04:18:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780367"], "description"=>"<p>The pedigree constructed around affected dogs indicates a likely recessive mode of inheritance as the affected dogs are born to unaffected parents and there are multiple affected littermates in some litter. The squared dogs were included in the GWAS. Individuals marked with yellow background were genotyped as obligatory carriers and were all heterozygous for the mutation.</p>", "links"=>[], "tags"=>["poag", "pcg", "Norwegian Elkhound", "mutation", "uk", "ADAMTS 10 biology", "387T", "ne", "glaucoma", "PCAG", "750 kb region", "novel missense mutation", "glaucoma gene"], "article_id"=>1229851, "categories"=>["Biological Sciences"], "users"=>["Saija J. Ahonen", "Maria Kaukonen", "Forrest D. Nussdorfer", "Christine D. Harman", "András M. Komáromy", "Hannes Lohi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0111941.g001", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pedigree_of_glaucoma_affected_Norwegian_Elkhounds_/1229851", "title"=>"Pedigree of glaucoma affected Norwegian Elkhounds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-11-05 04:18:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1780387", "https://ndownloader.figshare.com/files/1780388", "https://ndownloader.figshare.com/files/1780389", "https://ndownloader.figshare.com/files/1780390", "https://ndownloader.figshare.com/files/1780391"], "description"=>"<div><p>Primary glaucoma is one of the most common causes of irreversible blindness both in humans and in dogs. Glaucoma is an optic neuropathy affecting the retinal ganglion cells and optic nerve, and elevated intraocular pressure is commonly associated with the disease. Glaucoma is broadly classified into primary open angle (POAG), primary closed angle (PCAG) and primary congenital glaucoma (PCG). Human glaucomas are genetically heterogeneous and multiple loci have been identified. Glaucoma affects several dog breeds but only three loci and one gene have been implicated so far. We have investigated the genetics of primary glaucoma in the Norwegian Elkhound (NE). We established a small pedigree around the affected NEs collected from Finland, US and UK and performed a genome-wide association study with 9 cases and 8 controls to map the glaucoma gene to 750 kb region on canine chromosome 20 (p<sub>raw</sub> = 4.93×10<sup>−6</sup>, p<sub>genome</sub> = 0.025). The associated region contains a previously identified glaucoma gene, <i>ADAMTS10</i>, which was subjected to mutation screening in the coding regions. A fully segregating missense mutation (p.A387T) in exon 9 was found in 14 cases and 572 unaffected NEs (p<sub>Fisher</sub> = 3.5×10<sup>−27</sup>) with a high carrier frequency (25.3%). The mutation interrupts a highly conserved residue in the metalloprotease domain of ADAMTS10, likely affecting its functional capacity. Our study identifies the genetic cause of primary glaucoma in NEs and enables the development of a genetic test for breeding purposes. This study establishes also a new spontaneous canine model for glaucoma research to study the <i>ADAMTS10</i> biology in optical neuropathy.</p></div>", "links"=>[], "tags"=>["poag", "pcg", "Norwegian Elkhound", "mutation", "uk", "ADAMTS 10 biology", "387T", "ne", "glaucoma", "PCAG", "750 kb region", "novel missense mutation", "glaucoma gene"], "article_id"=>1229871, "categories"=>["Biological Sciences"], "users"=>["Saija J. Ahonen", "Maria Kaukonen", "Forrest D. Nussdorfer", "Christine D. Harman", "András M. Komáromy", "Hannes Lohi"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0111941.s001", "https://dx.doi.org/10.1371/journal.pone.0111941.s002", "https://dx.doi.org/10.1371/journal.pone.0111941.s003", "https://dx.doi.org/10.1371/journal.pone.0111941.s004", "https://dx.doi.org/10.1371/journal.pone.0111941.s005"], "stats"=>{"downloads"=>8, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Novel_Missense_Mutation_in_ADAMTS10_in_Norwegian_Elkhound_Primary_Glaucoma/1229871", "title"=>"A Novel Missense Mutation in <i>ADAMTS10</i> in Norwegian Elkhound Primary Glaucoma", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-11-05 04:18:28"}

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Relative Metric

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