Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci
Publication Date
February 03, 2017
Authors
Jacquelyn M. Evans, Rooksana E. Noorai, Kate L. Tsai, Alison N. Starr Moss, et al
Volume
13
Issue
2
Pages
e1006604
DOI
http://doi.org/10.1371/journal.pgen.1006604
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1006604
Scopus
85014115267
Mendeley
http://www.mendeley.com/research/beyond-mhc-canine-model-dermatomyositis-shows-complex-pattern-genetic-risk-involving-novel-loci
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Mendeley | Further Information

{"title"=>"Beyond the MHC: A canine model of dermatomyositis shows a complex pattern of genetic risk involving novel loci", "type"=>"journal", "authors"=>[{"first_name"=>"Jacquelyn M.", "last_name"=>"Evans", "scopus_author_id"=>"57193457063"}, {"first_name"=>"Rooksana E.", "last_name"=>"Noorai", "scopus_author_id"=>"47061817400"}, {"first_name"=>"Kate L.", "last_name"=>"Tsai", "scopus_author_id"=>"7201565912"}, {"first_name"=>"Alison N.", "last_name"=>"Starr-Moss", "scopus_author_id"=>"38962060300"}, {"first_name"=>"Cody M.", "last_name"=>"Hill", "scopus_author_id"=>"57193452093"}, {"first_name"=>"Kendall J.", "last_name"=>"Anderson", "scopus_author_id"=>"57193448095"}, {"first_name"=>"Thomas R.", "last_name"=>"Famula", "scopus_author_id"=>"7004017701"}, {"first_name"=>"Leigh Anne", "last_name"=>"Clark", "scopus_author_id"=>"7402667959"}], "year"=>2017, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"614651338", "pmid"=>"28158183", "doi"=>"10.1371/journal.pgen.1006604", "issn"=>"15537404", "scopus"=>"2-s2.0-85014115267", "sgr"=>"85014115267", "isbn"=>"1553-7404"}, "id"=>"a7a334b5-8550-3095-95dd-8463cf57734f", "abstract"=>"Author summary Juvenile dermatomyositis (JDM) is an autoimmune disease of the skin and muscle influenced by both genetic and environmental components. Although genes independent of the MHC are thought to contribute to disease pathogenesis, their identification has been complicated by a paucity of biological samples, disease heterogeneity, and genetically diverse subjects. A naturally occurring inflammatory disease of domestic dogs, also termed dermatomyositis (DMS), is analogous to JDM and is the only animal model available for genetic study. We first determined that, as in JDM, a particular MHC haplotype confers susceptibility to DMS. Capitalizing on the genetic isolation of dog breeds and extremely low MHC diversity within affected breeds, we used multibreed genome-wide association studies to identify two novel loci. Through genome resequencing and additional genotyping, we uncovered highly associated polymorphisms in conserved positions of PAN2 and MAP3K7CL. Analysis of three-locus genotypes revealed uniquely high frequencies among affected breeds and nine allelic combinations that confer moderate or high risk for DMS. The pattern of disease probability illustrates the presence of gene-gene interaction, as well as an inverse correlation between age of onset and number of risk alleles. This study highlights the utility of canine models for mapping susceptibility loci in complex diseases and detecting patterns of genetic interactions obscured in diverse human populations.", "link"=>"http://www.mendeley.com/research/beyond-mhc-canine-model-dermatomyositis-shows-complex-pattern-genetic-risk-involving-novel-loci", "reader_count"=>18, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Other"=>5, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Other"=>5, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>3, "Veterinary Science and Veterinary Medicine"=>9, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>9}}, "reader_count_by_country"=>{"Canada"=>1}, "group_count"=>1}

Scopus | Further Information

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