Gene Copy-Number Polymorphism Caused by Retrotransposition in Humans
Publication Date
January 24, 2013
Journal
PLOS Genetics
Authors
Daniel R. Schrider, Fabio C. P. Navarro, Pedro A. F. Galante, Raphael B. Parmigiani, et al
Volume
9
Issue
1
Pages
e1003242
DOI
https://dx.plos.org/10.1371/journal.pgen.1003242
Publisher URL
http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1003242
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23359205
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3554589
Europe PMC
http://europepmc.org/abstract/MED/23359205
Web of Science
000314651500078
Scopus
84873487706
Mendeley
http://www.mendeley.com/research/gene-copynumber-polymorphism-caused-retrotransposition-humans
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Mendeley | Further Information

{"title"=>"Gene Copy-Number Polymorphism Caused by Retrotransposition in Humans", "type"=>"journal", "authors"=>[{"first_name"=>"Daniel R.", "last_name"=>"Schrider", "scopus_author_id"=>"26322784200"}, {"first_name"=>"Fabio C.P.", "last_name"=>"Navarro", "scopus_author_id"=>"53981891200"}, {"first_name"=>"Pedro A.F.", "last_name"=>"Galante", "scopus_author_id"=>"6603534675"}, {"first_name"=>"Raphael B.", "last_name"=>"Parmigiani", "scopus_author_id"=>"8764167200"}, {"first_name"=>"Anamaria A.", "last_name"=>"Camargo", "scopus_author_id"=>"7005065206"}, {"first_name"=>"Matthew W.", "last_name"=>"Hahn", "scopus_author_id"=>"7201578309"}, {"first_name"=>"Sandro J.", "last_name"=>"de Souza", "scopus_author_id"=>"7102117085"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pmid"=>"23359205", "doi"=>"10.1371/journal.pgen.1003242", "pui"=>"368295358", "issn"=>"15537390", "sgr"=>"84873487706", "scopus"=>"2-s2.0-84873487706"}, "id"=>"23820e8f-f381-34d3-8981-2eb216a3fb2e", "abstract"=>"The era of whole-genome sequencing has revealed that gene copy-number changes caused by duplication and deletion events have important evolutionary, functional, and phenotypic consequences. Recent studies have therefore focused on revealing the extent of variation in copy-number within natural populations of humans and other species. These studies have found a large number of copy-number variants (CNVs) in humans, many of which have been shown to have clinical or evolutionary importance. For the most part, these studies have failed to detect an important class of gene copy-number polymorphism: gene duplications caused by retrotransposition, which result in a new intron-less copy of the parental gene being inserted into a random location in the genome. Here we describe a computational approach leveraging next-generation sequence data to detect gene copy-number variants caused by retrotransposition (retroCNVs), and we report the first genome-wide analysis of these variants in humans. We find that retroCNVs account for a substantial fraction of gene copy-number differences between any two individuals. Moreover, we show that these variants may often result in expressed chimeric transcripts, underscoring their potential for the evolution of novel gene functions. By locating the insertion sites of these duplicates, we are able to show that retroCNVs have had an important role in recent human adaptation, and we also uncover evidence that positive selection may currently be driving multiple retroCNVs toward fixation. Together these findings imply that retroCNVs are an especially important class of polymorphism, and that future studies of copy-number variation should search for these variants in order to illuminate their potential evolutionary and functional relevance.", "link"=>"http://www.mendeley.com/research/gene-copynumber-polymorphism-caused-retrotransposition-humans", "reader_count"=>115, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>6, "Researcher"=>31, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>33, "Student > Postgraduate"=>5, "Student > Master"=>15, "Other"=>4, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>10}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>6, "Researcher"=>31, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>33, "Student > Postgraduate"=>5, "Student > Master"=>15, "Other"=>4, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>10}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>17, "Agricultural and Biological Sciences"=>84, "Medicine and Dentistry"=>2, "Neuroscience"=>2, "Arts and Humanities"=>1, "Psychology"=>1, "Computer Science"=>4, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>2}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>84}, "Computer Science"=>{"Computer Science"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>17}, "Unspecified"=>{"Unspecified"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"Argentina"=>1, "Austria"=>1, "Hong Kong"=>1, "Belgium"=>1, "United States"=>8, "China"=>1, "Brazil"=>6, "United Kingdom"=>1, "France"=>2}, "group_count"=>2}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/500993"], "description"=>"*<p>Data from Emerson et al. <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003242#pgen.1003242-Emerson2\" target=\"_blank\">[29]</a>.</p>", "links"=>[], "tags"=>["retrogenes", "moving", "autosome", "chromosome", "autosomes", "vice-versa"], "article_id"=>171497, "categories"=>["Evolutionary Biology"], "users"=>["Daniel R. Schrider", "Fabio C. P. Navarro", "Pedro A. F. Galante", "Raphael B. Parmigiani", "Anamaria A. Camargo", "Matthew W. Hahn", "Sandro J. de Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003242.t001", "stats"=>{"downloads"=>4, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RetroCNVs_versus_fixed_retrogenes_moving_from_an_autosome_to_an_autosome_A_8594_A_from_the_X_chromosome_to_the_X_X_8594_X_from_the_X_to_the_autosomes_X_8594_A_or_vice_versa_A_8594_X_/171497", "title"=>"RetroCNVs versus fixed retrogenes moving from an autosome to an autosome (A→A) from the X chromosome to the X (X→X), from the X to the autosomes (X→A), or vice-versa (A→X).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-24 00:24:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/500726"], "description"=>"<p>Allele frequencies were calculated as described in the <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003242#s3\" target=\"_blank\">Materials and Methods</a>. RetroCNVs fixed in or absent from a given subpopulation are not shown.</p>", "links"=>[], "tags"=>["derived", "allele", "frequencies", "retrocnvs", "segregating"], "article_id"=>171238, "categories"=>["Evolutionary Biology"], "users"=>["Daniel R. Schrider", "Fabio C. P. Navarro", "Pedro A. F. Galante", "Raphael B. Parmigiani", "Anamaria A. Camargo", "Matthew W. Hahn", "Sandro J. de Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003242.g002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Estimated_derived_allele_frequencies_of_retroCNVs_segregating_in_three_human_subpopulations_/171238", "title"=>"Estimated derived allele frequencies of retroCNVs segregating in three human subpopulations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:20:38"}
  • {"files"=>["https://ndownloader.figshare.com/files/500870"], "description"=>"<p>π is shown in 10 kilobase windows for chromosomes containing the <i>DHFR</i> retroCNV (red) and those lacking this retroCNV (black). The location of the retroCNV insertion is marked by an arrow. While there is little difference in nucleotide diversity distal to the retroCNV, there is a recombination hotspot in that region (data from ref. <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003242#pgen.1003242-Frazer1\" target=\"_blank\">[65]</a>).</p>", "links"=>[], "tags"=>["nucleotide", "chromosome", "18", "chromosomes", "containing", "retrocnv"], "article_id"=>171380, "categories"=>["Evolutionary Biology"], "users"=>["Daniel R. Schrider", "Fabio C. P. Navarro", "Pedro A. F. Galante", "Raphael B. Parmigiani", "Anamaria A. Camargo", "Matthew W. Hahn", "Sandro J. de Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003242.g003", "stats"=>{"downloads"=>4, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduced_nucleotide_diversity_on_chromosome_18_among_chromosomes_containing_the_DHFR_retroCNV_in_CEU_/171380", "title"=>"Reduced nucleotide diversity on chromosome 18 among chromosomes containing the <i>DHFR</i> retroCNV in CEU.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:23:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/478098", "https://ndownloader.figshare.com/files/478100", "https://ndownloader.figshare.com/files/478101", "https://ndownloader.figshare.com/files/478103", "https://ndownloader.figshare.com/files/478105", "https://ndownloader.figshare.com/files/478106", "https://ndownloader.figshare.com/files/478107", "https://ndownloader.figshare.com/files/478109", "https://ndownloader.figshare.com/files/478110", "https://ndownloader.figshare.com/files/478111", "https://ndownloader.figshare.com/files/478113"], "description"=>"<div><p>The era of whole-genome sequencing has revealed that gene copy-number changes caused by duplication and deletion events have important evolutionary, functional, and phenotypic consequences. Recent studies have therefore focused on revealing the extent of variation in copy-number within natural populations of humans and other species. These studies have found a large number of copy-number variants (CNVs) in humans, many of which have been shown to have clinical or evolutionary importance. For the most part, these studies have failed to detect an important class of gene copy-number polymorphism: gene duplications caused by retrotransposition, which result in a new intron-less copy of the parental gene being inserted into a random location in the genome. Here we describe a computational approach leveraging next-generation sequence data to detect gene copy-number variants caused by retrotransposition (retroCNVs), and we report the first genome-wide analysis of these variants in humans. We find that retroCNVs account for a substantial fraction of gene copy-number differences between any two individuals. Moreover, we show that these variants may often result in expressed chimeric transcripts, underscoring their potential for the evolution of novel gene functions. By locating the insertion sites of these duplicates, we are able to show that retroCNVs have had an important role in recent human adaptation, and we also uncover evidence that positive selection may currently be driving multiple retroCNVs toward fixation. Together these findings imply that retroCNVs are an especially important class of polymorphism, and that future studies of copy-number variation should search for these variants in order to illuminate their potential evolutionary and functional relevance.</p> </div>", "links"=>[], "tags"=>["copy-number", "polymorphism", "caused", "retrotransposition", "humans"], "article_id"=>154210, "categories"=>["Evolutionary Biology"], "users"=>["Daniel R. Schrider", "Fábio Navarro", "Fabio C. P. Navarro", "Pedro A. F. Galante", "Raphael B. Parmigiani", "Anamaria A. Camargo", "Matthew W. Hahn", "Sandro J. de Souza"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003242.s001", "https://dx.doi.org/10.1371/journal.pgen.1003242.s002", "https://dx.doi.org/10.1371/journal.pgen.1003242.s003", "https://dx.doi.org/10.1371/journal.pgen.1003242.s004", "https://dx.doi.org/10.1371/journal.pgen.1003242.s005", "https://dx.doi.org/10.1371/journal.pgen.1003242.s006", "https://dx.doi.org/10.1371/journal.pgen.1003242.s007", "https://dx.doi.org/10.1371/journal.pgen.1003242.s008", "https://dx.doi.org/10.1371/journal.pgen.1003242.s009", "https://dx.doi.org/10.1371/journal.pgen.1003242.s010", "https://dx.doi.org/10.1371/journal.pgen.1003242.s011"], "stats"=>{"downloads"=>27, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Gene_Copy_Number_Polymorphism_Caused_by_Retrotransposition_in_Humans__/154210", "title"=>"Gene Copy-Number Polymorphism Caused by Retrotransposition in Humans", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-24 01:10:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/500634"], "description"=>"<p>a) RetroCNVs present in the reference genome are detected by searching for retrocopies in the reference that are absent from a sequenced individual, as revealed by paired-end reads spanning the location of the retroCNV and mapping too far apart from one another. b) RetroCNVs absent from the reference genome are detected by using paired-end reads to detect retroCNV insertion sites, and c) using reads that span exon-exon junctions but do not map to the reference genome.</p>", "links"=>[], "tags"=>["retrocnvs"], "article_id"=>171152, "categories"=>["Evolutionary Biology"], "users"=>["Daniel R. Schrider", "Fabio C. P. Navarro", "Pedro A. F. Galante", "Raphael B. Parmigiani", "Anamaria A. Camargo", "Matthew W. Hahn", "Sandro J. de Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003242.g001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detecting_retroCNVs_using_sequence_reads_/171152", "title"=>"Detecting retroCNVs using sequence reads.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-24 00:19:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/500946"], "description"=>"<p>RetroCNVs versus fixed retrocopies inserted in intronic versus intergenic sequence.</p>", "links"=>[], "tags"=>["retrocopies", "inserted", "intronic", "intergenic"], "article_id"=>171461, "categories"=>["Evolutionary Biology"], "users"=>["Daniel R. Schrider", "Fabio C. P. Navarro", "Pedro A. F. Galante", "Raphael B. Parmigiani", "Anamaria A. Camargo", "Matthew W. Hahn", "Sandro J. de Souza"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003242.t002", "stats"=>{"downloads"=>2, "page_views"=>81, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RetroCNVs_versus_fixed_retrocopies_inserted_in_intronic_versus_intergenic_sequence_/171461", "title"=>"RetroCNVs versus fixed retrocopies inserted in intronic versus intergenic sequence.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-01-24 00:24:21"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"25", "full-text"=>"24", "pdf"=>"12", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"22", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"20", "full-text"=>"24", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
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  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"11", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
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  • {"unique-ip"=>"11", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
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  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
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  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
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Relative Metric

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