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{"title"=>"Canine population structure: Assessment and impact of intra-breed stratification on SNP-based association studies", "type"=>"journal", "authors"=>[{"first_name"=>"Pascale", "last_name"=>"Quignon", "scopus_author_id"=>"6601957108"}, {"first_name"=>"Laetitia", "last_name"=>"Herbin", "scopus_author_id"=>"24503069000"}, {"first_name"=>"Edouard", "last_name"=>"Cadieu", "scopus_author_id"=>"6602304048"}, {"first_name"=>"Ewen F.", "last_name"=>"Kirkness", "scopus_author_id"=>"7005488078"}, {"first_name"=>"Benoit", "last_name"=>"Hédan", "scopus_author_id"=>"8219001900"}, {"first_name"=>"Dana S.", "last_name"=>"Mosher", "scopus_author_id"=>"16203348900"}, {"first_name"=>"Francis", "last_name"=>"Galibert", "scopus_author_id"=>"7102327721"}, {"first_name"=>"Catherine", "last_name"=>"André", "scopus_author_id"=>"57192709362"}, {"first_name"=>"Elaine A.", "last_name"=>"Ostrander", "scopus_author_id"=>"35377190600"}, {"first_name"=>"Christophe", "last_name"=>"Hitte", "scopus_author_id"=>"6603672763"}], "year"=>2007, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-44349105228", "sgr"=>"44349105228", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0001324", "pmid"=>"18091995", "isbn"=>"1932-6203 (Electronic)", "pui"=>"351736597"}, "id"=>"066268dc-b51e-3090-b60c-5e52c0ddc648", "abstract"=>"BACKGROUND: In canine genetics, the impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogs of a single breed, usually from the same country or geographic area. However one way to increase the power of genetic studies is to sample individuals of the same breed but from different geographic areas, with the expectation that independent meiotic events will have shortened the presumed ancestral haplotype around the mutation differently. Little is known, however, about genetic variation among dogs of the same breed collected from different geographic regions. METHODOLOGY/PRINCIPAL FINDINGS: In this report, we address the magnitude and impact of genetic diversity among common breeds sampled in the U.S. and Europe. The breeds selected, including the Rottweiler, Bernese mountain dog, flat-coated retriever, and golden retriever, share susceptibility to a class of soft tissue cancers typified by malignant histiocytosis in the Bernese mountain dog. We genotyped 722 SNPs at four unlinked loci (between 95 and 271 per locus) on canine chromosome 1 (CFA1). We showed that each population is characterized by distinct genetic diversity that can be correlated with breed history. When the breed studied has a reduced intra-breed diversity, the combination of dogs from international locations does not increase the rate of false positives and potentially increases the power of association studies. However, over-sampling cases from one geographic location is more likely to lead to false positive results in breeds with significant genetic diversity. CONCLUSIONS: These data provide new guidelines for association studies using purebred dogs that take into account population structure.", "link"=>"http://www.mendeley.com/research/canine-population-structure-assessment-impact-intrabreed-stratification-snpbased-association-studies", "reader_count"=>67, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>6, "Researcher"=>16, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>3, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>6, "Researcher"=>16, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>3, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>7, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Environmental Science"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>39, "Medicine and Dentistry"=>10, "Arts and Humanities"=>2, "Philosophy"=>1, "Veterinary Science and Veterinary Medicine"=>4, "Psychology"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>39}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>2}, "Philosophy"=>{"Philosophy"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>4}}, "reader_count_by_country"=>{"Sweden"=>1, "Hungary"=>1, "United States"=>3, "Egypt"=>1, "Italy"=>1, "Australia"=>1, "France"=>2, "Spain"=>1}, "group_count"=>2}

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• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/60251450-b752-460d-a548-4483b8576fc5", "title"=>"Why would this be?", "body"=>"I'm certain the authors can explain, but I would like to know why.", "highlightedText"=>"''one GR remaining as an outlier''\nhttp://plosone.org/article/info:doi/10.1371/journal.pone.0001324#article1.body1.sec2.sec6.p1", "isRemoved"=>false, "created"=>"2007-12-21T00:58:14Z", "lastModified"=>"2007-12-21T00:58:14Z", "creator"=>{"userId"=>"94889"}, "competingInterestStatement"=>{"creatorWasPrompted"=>false, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0001324", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2007-12-21T00:58:14Z", "replies"=>[]}
• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/b023d1a8-5e6e-4d26-946a-e429fc44e93c", "title"=>"How would this work across different 'kinds' of breeds?", "body"=>"One question that comes to mind immediately for me is the difference between breeds that are, essentially, offshoots of some basic stock vs. breeds that are amalgams of multiple breeds. One could say that to some extent both are true of all breeds, but I think that would be wrong. For instance, the mountain dogs such as the Bernese and the Pyrenees are probably bred from Tibetan mastiffs more or less directly, thus involving a reduction in genetic variation within the breed. In contract, the Newfoundland is also bred from a mastiff stock but possibly with another very distantly related breed added in for special effect (thus offsetting the variation). The doberman is one of the most complex breeds of recent times, with several different breeds used to achieve a true breeding highly specialized form. Breeds that derive mainly from divergence should have different patterns (genetically) than breeds derived from combinatorial breeding. \n\n<a href=\"http://scienceblogs.com/gregladen/2008/05/evolutionary_genetics_of_canin.php\">(I've blogged about this paper here)</a>", "isRemoved"=>false, "created"=>"2008-05-06T15:44:34Z", "lastModified"=>"2008-05-06T15:44:34Z", "creator"=>{"userId"=>"164199"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>false, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pone.0001324", "state"=>"published", "journals"=>{"PLoSONE"=>{"journalKey"=>"PLoSONE", "eIssn"=>"1932-6203", "title"=>"PLOS ONE"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2008-05-06T15:44:34Z", "replies"=>[]}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/940221"], "description"=>"<p>Number of shared and specific haplotypes between the US and European subpopulations for each breed.</p>", "links"=>[], "tags"=>["haplotypes", "european", "subpopulations"], "article_id"=>610651, "categories"=>["Genetics"], "users"=>["Pascale Quignon", "Laetitia Herbin", "Edouard Cadieu", "Ewen F. Kirkness", "Benoit Hédan", "Dana S. Mosher", "Francis Galibert", "Catherine André", "Elaine A. Ostrander", "Christophe Hitte"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001324.t003", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_shared_and_specific_haplotypes_between_the_US_and_European_subpopulations_for_each_breed_/610651", "title"=>"Number of shared and specific haplotypes between the US and European subpopulations for each breed.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-12-19 00:10:51"}
• {"files"=>["https://ndownloader.figshare.com/files/940292"], "description"=>"1<p>equal or similar proportion of ‘causal’ genotype, (i.e. four to six “cases” in each sub-populations).</p>2<p>‘causal’ genotype from one sub-population only.</p>", "links"=>[], "tags"=>["snps", "p-value", "mb", "causative"], "article_id"=>610722, "categories"=>["Genetics"], "users"=>["Pascale Quignon", "Laetitia Herbin", "Edouard Cadieu", "Ewen F. Kirkness", "Benoit Hédan", "Dana S. Mosher", "Francis Galibert", "Catherine André", "Elaine A. Ostrander", "Christophe Hitte"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001324.t004", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentage_of_SNPs_with_p_value_lt_0_05_located_beyond_5_Mb_of_a_causative_SNP_/610722", "title"=>"Percentage of SNPs with p-value <0.05 located beyond 5 Mb of a causative SNP.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-12-19 00:12:02"}
• {"files"=>["https://ndownloader.figshare.com/files/940013"], "description"=>"<p>Clustering of the 119 dogs (k = 4) from the four different breeds. In the dendogram each vertical line represents a single dog and the color reflects the four clusters obtained by PLINK analysis. A grey dashed line indicates an outlier dog. Below the dendogram, dogs are named by their breed origin, and names are colored upon their cluster assignment. At the bottom of the figure, colored squares are drawn on four lines, each line representing the different breeds. The scale on the right axis represents the genetics distances calculated by PLINK software. Each breed separates from the others as the four colors correspond exactly to the four breeds, red for BMD, blue for FCR, black for GR and green for ROT.</p>", "links"=>[], "tags"=>["clustering"], "article_id"=>610448, "categories"=>["Genetics"], "users"=>["Pascale Quignon", "Laetitia Herbin", "Edouard Cadieu", "Ewen F. Kirkness", "Benoit Hédan", "Dana S. Mosher", "Francis Galibert", "Catherine André", "Elaine A. Ostrander", "Christophe Hitte"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001324.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hierarchical_clustering_between_the_four_breeds_/610448", "title"=>"Hierarchical clustering between the four breeds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-12-19 00:07:28"}
• {"files"=>["https://ndownloader.figshare.com/files/940182"], "description"=>"1<p>Values are calculated based on 722 genotypes of dogs from Europe and US. Interval of 95% confidence of bootstrapping are in parenthesis.</p>", "links"=>[], "tags"=>["distances", "inter"], "article_id"=>610616, "categories"=>["Genetics"], "users"=>["Pascale Quignon", "Laetitia Herbin", "Edouard Cadieu", "Ewen F. Kirkness", "Benoit Hédan", "Dana S. Mosher", "Francis Galibert", "Catherine André", "Elaine A. Ostrander", "Christophe Hitte"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001324.t002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_distances_F_ST_inter_and_intra_breed_/610616", "title"=>"Genetic distances (F_ST) inter and intra-breed.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-12-19 00:10:16"}
• {"files"=>["https://ndownloader.figshare.com/files/463025", "https://ndownloader.figshare.com/files/463033", "https://ndownloader.figshare.com/files/463045", "https://ndownloader.figshare.com/files/463051", "https://ndownloader.figshare.com/files/463060"], "description"=>"<div><h3>Background</h3><p>In canine genetics, the impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogs of a single breed, usually from the same country or geographic area. However one way to increase the power of genetic studies is to sample individuals of the same breed but from different geographic areas, with the expectation that independent meiotic events will have shortened the presumed ancestral haplotype around the mutation differently. Little is known, however, about genetic variation among dogs of the same breed collected from different geographic regions.</p><h3>Methodology/Principal Findings</h3><p>In this report, we address the magnitude and impact of genetic diversity among common breeds sampled in the U.S. and Europe. The breeds selected, including the Rottweiler, Bernese mountain dog, flat-coated retriever, and golden retriever, share susceptibility to a class of soft tissue cancers typified by malignant histiocytosis in the Bernese mountain dog. We genotyped 722 SNPs at four unlinked loci (between 95 and 271 per locus) on canine chromosome 1 (CFA1). We showed that each population is characterized by distinct genetic diversity that can be correlated with breed history. When the breed studied has a reduced intra-breed diversity, the combination of dogs from international locations does not increase the rate of false positives and potentially increases the power of association studies. However, over-sampling cases from one geographic location is more likely to lead to false positive results in breeds with significant genetic diversity.</p><h3>Conclusions</h3><p>These data provide new guidelines for association studies using purebred dogs that take into account population structure.</p></div>", "links"=>[], "tags"=>["canine", "intra-breed", "stratification", "snp-based", "studies"], "article_id"=>151254, "categories"=>["Genetics"], "users"=>["Pascale Quignon", "Laetitia Herbin", "Edouard Cadieu", "Ewen F. Kirkness", "Benoit Hédan", "Dana S. Mosher", "Francis Galibert", "Catherine André", "Elaine A. Ostrander", "Christophe Hitte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0001324.s001", "https://dx.doi.org/10.1371/journal.pone.0001324.s002", "https://dx.doi.org/10.1371/journal.pone.0001324.s003", "https://dx.doi.org/10.1371/journal.pone.0001324.s004", "https://dx.doi.org/10.1371/journal.pone.0001324.s005"], "stats"=>{"downloads"=>10, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Canine_Population_Structure_Assessment_and_Impact_of_Intra_Breed_Stratification_on_SNP_Based_Association_Studies/151254", "title"=>"Canine Population Structure: Assessment and Impact of Intra-Breed Stratification on SNP-Based Association Studies", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2007-12-19 00:20:54"}
• {"files"=>["https://ndownloader.figshare.com/files/940109"], "description"=>"<p>The figure shows the clustering analysis (k = 2) within each breed for BMD, FCR, ROT and GR (n = 30 for each breed). For each breed, a dendogram is drawn in which each vertical line represents a single dog. The two clusters are represented in blue and red, and grey dashed lines indicate outlier dogs. Below the dendogram, dogs are named by geographical origin (US or EU), and names are colored upon their cluster assignment. The scale on the right axis represents the genetics distances calculated by PLINK software.</p>", "links"=>[], "tags"=>["clustering"], "article_id"=>610546, "categories"=>["Genetics"], "users"=>["Pascale Quignon", "Laetitia Herbin", "Edouard Cadieu", "Ewen F. Kirkness", "Benoit Hédan", "Dana S. Mosher", "Francis Galibert", "Catherine André", "Elaine A. Ostrander", "Christophe Hitte"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001324.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hierarchical_clustering_within_breeds_/610546", "title"=>"Hierarchical clustering within breeds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2007-12-19 00:09:06"}
• {"files"=>["https://ndownloader.figshare.com/files/940252"], "description"=>"1<p>Bernese mountain dogs.</p>2<p>Flat-coated retrievers.</p>3<p>Golden retrievers.</p>4<p>Rottweilers.</p>5<p>observed heterozygosity.</p>6<p>expected heterozygosity.</p>7<p>percentage of SNP rejecting Hardy-Weinberg equilibrium.</p>", "links"=>[], "tags"=>["frequencies", "722", "snps"], "article_id"=>610687, "categories"=>["Genetics"], "users"=>["Pascale Quignon", "Laetitia Herbin", "Edouard Cadieu", "Ewen F. Kirkness", "Benoit Hédan", "Dana S. Mosher", "Francis Galibert", "Catherine André", "Elaine A. Ostrander", "Christophe Hitte"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0001324.t001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allele_frequencies_of_the_722_SNPs_for_the_four_breeds_/610687", "title"=>"Allele frequencies of the 722 SNPs for the four breeds.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2007-12-19 00:11:27"}

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Relative Metric

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F1000Prime