Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus
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{"title"=>"Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus", "type"=>"journal", "authors"=>[{"first_name"=>"Saija J.", "last_name"=>"Ahonen", "scopus_author_id"=>"6603360752"}, {"first_name"=>"Elina", "last_name"=>"Pietilä", "scopus_author_id"=>"55818135900"}, {"first_name"=>"Cathryn S.", "last_name"=>"Mellersh", "scopus_author_id"=>"35502197800"}, {"first_name"=>"Katriina", "last_name"=>"Tiira", "scopus_author_id"=>"6507108586"}, {"first_name"=>"Liz", "last_name"=>"Hansen", "scopus_author_id"=>"7401576180"}, {"first_name"=>"Gary S.", "last_name"=>"Johnson", "scopus_author_id"=>"57193139518"}, {"first_name"=>"Hannes", "last_name"=>"Lohi", "scopus_author_id"=>"6602309083"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84881356404", "sgr"=>"84881356404", "pui"=>"369535386", "isbn"=>"10.1371/journal.pone.0070903", "pmid"=>"23951034", "doi"=>"10.1371/journal.pone.0070903"}, "id"=>"324e17b4-aac0-3a92-b9d5-848e2a42d4ca", "abstract"=>"Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG), primary open-angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively) in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63 × 10(-10), OR = 32 for homozygosity). Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease.", "link"=>"http://www.mendeley.com/research/genomewide-association-study-identifies-novel-canine-glaucoma-locus-1", "reader_count"=>18, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>4, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>4, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>10, "Medicine and Dentistry"=>4, "Veterinary Science and Veterinary Medicine"=>2, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>10}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>2}}, "reader_count_by_country"=>{"Finland"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1146094"], "description"=>"<p>Number and percentage of dogs with different degrees of PLD.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Genetics of disease", "Genome-wide association studies", "ophthalmology", "glaucoma", "Animal types", "Small animals", "Veterinary anatomy and physiology", "Animal ocular anatomy", "Veterinary medicine", "Veterinary opthalmology", "Veterinary pathology"], "article_id"=>766853, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Saija J. Ahonen", "Elina Pietilä", "Cathryn S. Mellersh", "Katriina Tiira", "Liz Hansen", "Gary S. Johnson", "Hannes Lohi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0070903.t002", "stats"=>{"downloads"=>4, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Degrees_of_PLD_/766853", "title"=>"Degrees of PLD.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-07 02:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1146095"], "description"=>"<p>Categorization of PLD severity based on the percentage of abnormal PL.</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Genetics of disease", "Genome-wide association studies", "ophthalmology", "glaucoma", "Animal types", "Small animals", "Veterinary anatomy and physiology", "Animal ocular anatomy", "Veterinary medicine", "Veterinary opthalmology", "Veterinary pathology", "pld"], "article_id"=>766854, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Saija J. Ahonen", "Elina Pietilä", "Cathryn S. Mellersh", "Katriina Tiira", "Liz Hansen", "Gary S. Johnson", "Hannes Lohi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0070903.t001", "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Categorization_of_PLD_severity_/766854", "title"=>"Categorization of PLD severity.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-08-07 02:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1146093"], "description"=>"<p><b>A</b>) A Manhattan plot of genome-wide case-control association analysis performed using 23 cases and 23 controls. <b>B</b>) Results of the genome-wide association analysis after 50,000 permutations. A significant association was identified on CFA8 (P = 5.83×10−6, Pgenome = 5.5×10−3). Horizontal line indicate the 5% significance level <b>C</b>) The glaucoma associated region on CFA8 spans from 20.0 Mb to 29.5 Mb. <b>D</b>) Results of the fine-mapping narrowed the best association to 22.0 and 23.6 Mb (P = 1.63×10−10). Gray line shows the individual SNP association, black line indicates the 5-SNP haplotype. <b>E</b>) The canine CFA8 locus (solid black line) maps to a human chromosome 14 to a 11 Mb region between 39.2 Mb to 50.4 Mb. Previously mapped GLC3C locus for PCG between 77.4 Mb to 78.6 Mb, maps to canine CFA8 at a region between 52.8 Mb to 53.9 Mb (dashed black line). Another PCG locus was mapped on chr14 between 71.5 Mb to 78.6 Mb which overlap the GLC3C locus (solid blue line). Two POAG loci were mapped on chr14 between 20.8–33.97 Mb (dotted black line) and a QTL locus between 60.79–61.0 Mb (dashed red line).</p>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Genetics of disease", "Genome-wide association studies", "ophthalmology", "glaucoma", "Animal types", "Small animals", "Veterinary anatomy and physiology", "Animal ocular anatomy", "Veterinary medicine", "Veterinary opthalmology", "Veterinary pathology"], "article_id"=>766852, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Saija J. Ahonen", "Elina Pietilä", "Cathryn S. Mellersh", "Katriina Tiira", "Liz Hansen", "Gary S. Johnson", "Hannes Lohi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0070903.g001", "stats"=>{"downloads"=>2, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genome_wide_association_analysis_/766852", "title"=>"Genome wide association analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-08-07 02:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/1146098", "https://ndownloader.figshare.com/files/1146099", "https://ndownloader.figshare.com/files/1146101", "https://ndownloader.figshare.com/files/1146102", "https://ndownloader.figshare.com/files/1146103"], "description"=>"<div><p>Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its hereditary forms are classified into primary closed-angle (PCAG), primary open-angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been mapped in human, only a few genes have been identified that are associated with the development of glaucoma and the genetic basis of the disease remains poorly understood. Glaucoma has also been described in many dog breeds, including Dandie Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We designed clinical and genetic studies to better define the clinical features of glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was based on ophthalmic examinations of the affected dogs and 18 additionally investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome wide association study was performed in a cohort of 23 affected and 23 controls, followed by a fine mapping, a replication study and candidate gene sequencing. The clinical study suggested that ocular abnormalities including abnormal iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%, respectively) in the breed and the disease resembles human PCAG. The genetic study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb best associated region (p = 1.63×10<sup>−10</sup>, OR = 32 for homozygosity). Mutation screening in five candidate genes did not reveal any causative variants. This study indicates that although ocular abnormalities are common in DDTs, the genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus shares synteny to a region in human chromosome 14q, which harbors several loci associated with POAG and PCG. Our study reveals a new locus for canine glaucoma and ongoing molecular studies will likely help to understand the genetic etiology of the disease.</p></div>", "links"=>[], "tags"=>["genetics", "Animal genetics", "Genetics of disease", "Genome-wide association studies", "ophthalmology", "glaucoma", "Animal types", "Small animals", "Veterinary anatomy and physiology", "Animal ocular anatomy", "Veterinary medicine", "Veterinary opthalmology", "Veterinary pathology", "identifies", "canine"], "article_id"=>766857, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Saija J. Ahonen", "Elina Pietilä", "Cathryn S. Mellersh", "Katriina Tiira", "Liz Hansen", "Gary S. Johnson", "Hannes Lohi"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0070903.s001", "https://dx.doi.org/10.1371/journal.pone.0070903.s002", "https://dx.doi.org/10.1371/journal.pone.0070903.s003", "https://dx.doi.org/10.1371/journal.pone.0070903.s004", "https://dx.doi.org/10.1371/journal.pone.0070903.s005"], "stats"=>{"downloads"=>15, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genome_Wide_Association_Study_Identifies_a_Novel_Canine_Glaucoma_Locus_/766857", "title"=>"Genome-Wide Association Study Identifies a Novel Canine Glaucoma Locus", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-08-07 02:25:22"}

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