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• {"link"=>{"url"=>"http://www.citeulike.org/group/10570/article/11434898"}, "post_time"=>"2012-10-11 10:14:23", "tag"=>["genetics", "human", "staffpaper"], "linkout"=>{"type"=>"DOI", "url"=>"http://dx.doi.org/10.1371/journal.pgen.1002903"}, "group"=>"Journal picks", "group_id"=>"10570", "article_id"=>"11434898"}
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{"title"=>"Rare Copy Number Variants Contribute to Congenital Left-Sided Heart Disease", "type"=>"journal", "authors"=>[{"first_name"=>"Marc Phillip", "last_name"=>"Hitz", "scopus_author_id"=>"56185773800"}, {"first_name"=>"Louis Philippe", "last_name"=>"Lemieux-Perreault", "scopus_author_id"=>"55371462600"}, {"first_name"=>"Christian", "last_name"=>"Marshall", "scopus_author_id"=>"7201903397"}, {"first_name"=>"Yassamin", "last_name"=>"Feroz-Zada", "scopus_author_id"=>"35331967000"}, {"first_name"=>"Robbie", "last_name"=>"Davies", "scopus_author_id"=>"55370994500"}, {"first_name"=>"Shi Wei", "last_name"=>"Yang", "scopus_author_id"=>"56698933900"}, {"first_name"=>"Anath Christopher", "last_name"=>"Lionel", "scopus_author_id"=>"23393441400"}, {"first_name"=>"Guylaine", "last_name"=>"D'Amours", "scopus_author_id"=>"37261078800"}, {"first_name"=>"Emmanuelle", "last_name"=>"Lemyre", "scopus_author_id"=>"55913639800"}, {"first_name"=>"Rebecca", "last_name"=>"Cullum", "scopus_author_id"=>"10340701900"}, {"first_name"=>"Jean Luc", "last_name"=>"Bigras", "scopus_author_id"=>"6603947021"}, {"first_name"=>"Maryse", "last_name"=>"Thibeault", "scopus_author_id"=>"54411355400"}, {"first_name"=>"Philippe", "last_name"=>"Chetaille", "scopus_author_id"=>"6602257248"}, {"first_name"=>"Alexandre", "last_name"=>"Montpetit", "scopus_author_id"=>"6603250038"}, {"first_name"=>"Paul", "last_name"=>"Khairy", "scopus_author_id"=>"6603925410"}, {"first_name"=>"Bert", "last_name"=>"Overduin", "scopus_author_id"=>"57189011455"}, {"first_name"=>"Sabine", "last_name"=>"Klaassen", "scopus_author_id"=>"24338568000"}, {"first_name"=>"Pamela", "last_name"=>"Hoodless", "scopus_author_id"=>"6602719972"}, {"first_name"=>"Mona", "last_name"=>"Nemer", "scopus_author_id"=>"7006091355"}, {"first_name"=>"Alexandre F.R.", "last_name"=>"Stewart", "scopus_author_id"=>"56962727600"}, {"first_name"=>"Cornelius", "last_name"=>"Boerkoel", "scopus_author_id"=>"6701809729"}, {"first_name"=>"Stephen W.", "last_name"=>"Scherer", "scopus_author_id"=>"35374654500"}, {"first_name"=>"Andrea", "last_name"=>"Richter", "scopus_author_id"=>"7401645844"}, {"first_name"=>"Marie Pierre", "last_name"=>"Dubé", "scopus_author_id"=>"7103243627"}, {"first_name"=>"Gregor", "last_name"=>"Andelfinger", "scopus_author_id"=>"6603437102"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-84866915849", "sgr"=>"84866915849", "pui"=>"365755968", "isbn"=>"10.1371/journal.pgen.1002903", "pmid"=>"22969434", "doi"=>"10.1371/journal.pgen.1002903"}, "id"=>"f03b78b1-ac49-3448-a400-40a02e61ff04", "abstract"=>"Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59 multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as SMC1A, MFAP4, and CTHRC1, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and de novo events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology.", "link"=>"http://www.mendeley.com/research/rare-copy-number-variants-contribute-congenital-leftsided-heart-disease", "reader_count"=>78, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Student > Doctoral Student"=>8, "Researcher"=>26, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>3, "Other"=>4, "Student > Master"=>5, "Student > Bachelor"=>3, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>6, "Student > Doctoral Student"=>8, "Researcher"=>26, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>3, "Other"=>4, "Student > Master"=>5, "Student > Bachelor"=>3, "Lecturer"=>2, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>18, "Medicine and Dentistry"=>22, "Agricultural and Biological Sciences"=>28, "Neuroscience"=>2, "Physics and Astronomy"=>1, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>22}, "Neuroscience"=>{"Neuroscience"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>18}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Canada"=>1, "Hong Kong"=>1, "Germany"=>1}, "group_count"=>5}

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• {"id"=>"243821754286497792", "text"=>"#PLoS #Genetics: Rare Copy Number Variants Contribute to Congenital Left-Sided Heart Disease http://t.co/3K1u8rLi", "created_at"=>"2012-09-06T21:23:30Z", "user"=>"whatDNAtest", "user_name"=>"Carlos Esteban PhD", "user_profile_image"=>"http://a0.twimg.com/profile_images/2209463838/c-azul-negro2_normal.jpg"}
• {"id"=>"243821792609837056", "text"=>"PLoSGenetics: Rare Copy Number Variants Contribute to Congenital Left-Sided Heart Disease: by Marc-Phillip Hitz,... http://t.co/GUQ3z8kF", "created_at"=>"2012-09-06T21:23:40Z", "user"=>"genomigence", "user_name"=>"genomigence", "user_profile_image"=>"http://a0.twimg.com/profile_images/570906209/tree_normal.png"}
• {"id"=>"243832428286853120", "text"=>"RT @whatDNAtest: #PLoS #Genetics: Rare Copy Number Variants Contribute to Congenital Left-Sided Heart Disease http://t.co/3K1u8rLi", "created_at"=>"2012-09-06T22:05:55Z", "user"=>"GlamorganGPU", "user_name"=>"Genomics Policy Unit", "user_profile_image"=>"http://a0.twimg.com/profile_images/915592828/GPUlogo_normal.jpg"}
• {"id"=>"244304221728559104", "text"=>"Rare Copy Number Variants Contribute to Congenital Left-Sided Heart Disease http://t.co/zW3QauQT\"#bahrain#cardiac", "created_at"=>"2012-09-08T05:20:40Z", "user"=>"annemostafa", "user_name"=>"Bahrainpsychologist", "user_profile_image"=>"http://a0.twimg.com/profile_images/2574130304/ib4w9o8gmj2mcllqytud_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/580535"], "description"=>"<p>(a, b). <i>In situ</i> hybridizations for <i>MFAP4</i> of a sagittal section of a wild-type stage E 14.5 mouse heart (c, d) <i>In situ</i> hybridizations for <i>CTHRC1</i> of a sagittal section of a wild-type stage E 14.5 mouse heart. Both assays show a strong expression in the pulmonary valve (arrows) and aortic/mitral valve (arrowheads). Unlike <i>CTHRC1</i> which is more restricted to the valves and only weakly expressed in the endothelium of the aorta, <i>MFAP4</i> shows a strong expression in the pulmonary artery and ascending aorta (asterisks). Pictures are taken from Eurexpress (<a href=\"http://www.eurexpress.org\" target=\"_blank\">www.eurexpress.org</a>).</p>", "links"=>[], "tags"=>["embryonic"], "article_id"=>251006, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002903.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_mRNA_expression_profile_of_CTHRC1_and_MFAP4_in_embryonic_mouse_heart_/251006", "title"=>"mRNA expression profile of <i>CTHRC1</i> and <i>MFAP4</i> in embryonic mouse heart.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:16:46"}
• {"files"=>["https://ndownloader.figshare.com/files/580827"], "description"=>"<p>(a,b) FISH was performed on metaphase chromosomes obtained from peripheral blood with a labeled BAC clone that mapped within the detected copy gain (RP11-52N6, red) and a control probe mapped to the Xp/Yp pseudoautosomal region of the sex chromosomes (DXYS129 & DXYS153, green). Green dots show the control probe hybridized to the p arm of chromosomes X and Y. Red dots show the RP11-52N6 BAC clone hybridized on chromosome X (white arrow heads) and in the heterochromatin of chromosome 9 (white arrows). A star shows the normal chromosome 9. These results show that the copy gain is due to a der(9)ins(X;9)(p11.22;q12) in both the father (a) and his son (b). (c). Chromosomal region of the insertion (X;9)(p11.22;q12) in the father and the son of family 5. Four RefSeq genes are identified within this <i>region IQSEC2, RIBC2, HSD17B10</i> and the Cornelia de Lange gene <i>SMC1A</i>. One larger and one smaller CNV have been detected in the DGV database in this region.</p>", "links"=>[], "tags"=>["genetics and genomics", "pediatrics and child health"], "article_id"=>251291, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002903.g004", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Karyotype_der_9_ins_X_9_p11_22_q12_in_family_5_/251291", "title"=>"Karyotype der(9)ins(X;9)(p11.22;q12) in family 5.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:21:31"}
• {"files"=>["https://ndownloader.figshare.com/files/581149"], "description"=>"<p>Distribution of isolated and combined LS-CHD phenotypes. Percents are relative to the total of 174 individuals with cardiovascular malformation.</p>*<p>This number includes one case with hypoplastic left heart syndrome.</p>", "links"=>[], "tags"=>["genetics and genomics", "pediatrics and child health"], "article_id"=>251610, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002903.t001", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overview_over_lesions_/251610", "title"=>"Overview over lesions.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-06 00:26:50"}
• {"files"=>["https://ndownloader.figshare.com/files/580413"], "description"=>"<p>Flowchart of sample analysis from recruitment to prioritization.</p>", "links"=>[], "tags"=>["overview", "workflow", "cnv"], "article_id"=>250874, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002903.g001", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_overview_of_the_workflow_for_CNV_detection_/250874", "title"=>"Summary overview of the workflow for CNV detection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:14:34"}
• {"files"=>["https://ndownloader.figshare.com/files/580695"], "description"=>"<p>See legend at the bottom of the figure for explanation of symbols. DNA numbers refer to Tables S1, S2, S3, S4, S5, S6, S7, S8, S9 for affected individuals in whom rare CNVs were identified. A.) In family 5, we identified a maternally inherited gain overlapping <i>PXDNL</i> and a paternally inherited insertion der(9)ins(X;9)(p11.22;q12) overlapping the Cornelia de Lange syndrome gene SMC1A in the severely affected propositus.(NB: Individual 2126 was not initially genotyped on the Affymetrix 6.0 panel and is therefore not described). B.) The severely affected propositus in family 54 showed three different rare CNVs: a paternally inherited gain overlapping SEMA5B, HSPBAP1, DIRC2 and PARP14, a paternally inherited loss of LIMS1, and a <i>de novo</i> partial duplication on chromosome1q21.1. C.) <i>De novo</i> occurrence and non-transmission of a large CNV gain (3817 kb) on chr4p16 overlapping the Ellis van Creveld region on chromosome 4. D.), E.) F.) Segregation of prioritized CNVs with disease in families 18, 21 and 39.</p>", "links"=>[], "tags"=>["segregation", "patterns", "cnvs", "ls-chd"], "article_id"=>251157, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002903.g003", "stats"=>{"downloads"=>8, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selected_segregation_patterns_of_CNVs_in_LS_CHD_pedigrees_/251157", "title"=>"Selected segregation patterns of CNVs in LS-CHD pedigrees.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:19:17"}
• {"files"=>["https://ndownloader.figshare.com/files/580972"], "description"=>"<p>FISH was performed on metaphase chromosomes and nuclei obtained from peripheral blood with a labeled BAC clone mapped within the detected copy gain (RP11-89K12, green) and a control probe mapped to 4p14 (RP11-332F10, red). (a) Two series of adjacent green dots show the extra copy of the duplicated segment on chromosome 4. (b) The nucleus view with the three green dots showing three copies of the region overlapping the Ellis van Creveld genes on chromosome 4 (c) Log 2 ratio for the large gain in Family 43 on chromosome 4. In general, dots are scattered around 0 along the x-axis for, whereas the identified gain leads to a clear upward shift (d) Heatmap of the identified gain on chromosome 4, each line refers to one individual. An orange row indicates two copies of the region whereas an extra copy leads to a gain in the intensity (yellow line for the individual in family 43).</p>", "links"=>[], "tags"=>["genetics and genomics", "pediatrics and child health"], "article_id"=>251430, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002903.g005", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_dup_4_p16_1_in_family_43_/251430", "title"=>"dup(4)(p16.1) in family 43.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-06 00:23:50"}
• {"files"=>["https://ndownloader.figshare.com/files/581218"], "description"=>"<p>Compilation of the 25 LS-CHD candidate genes fulfilling all selection criteria. From left to right: gene name; ENDEAVOUR <i>in silico</i> prioritization; fold overexpression in SAGE experiments outflow tract versus atria/ventricles; <i>in situ</i> hybridization in mouse hearts at embryonic day E10.5; transmission pattern (individual IDs); genomic location.</p>", "links"=>[], "tags"=>["genetics and genomics", "pediatrics and child health"], "article_id"=>251682, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002903.t002", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identified_candidate_genes_/251682", "title"=>"Identified candidate genes.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-09-06 00:28:02"}
• {"files"=>["https://ndownloader.figshare.com/files/306803", "https://ndownloader.figshare.com/files/306840", "https://ndownloader.figshare.com/files/307011", "https://ndownloader.figshare.com/files/307083", "https://ndownloader.figshare.com/files/307128", "https://ndownloader.figshare.com/files/307166", "https://ndownloader.figshare.com/files/307185", "https://ndownloader.figshare.com/files/307205", "https://ndownloader.figshare.com/files/307223", "https://ndownloader.figshare.com/files/307245", "https://ndownloader.figshare.com/files/307266", "https://ndownloader.figshare.com/files/307289", "https://ndownloader.figshare.com/files/307315", "https://ndownloader.figshare.com/files/307344"], "description"=>"<div><p>Left-sided congenital heart disease (CHD) encompasses a spectrum of malformations that range from bicuspid aortic valve to hypoplastic left heart syndrome. It contributes significantly to infant mortality and has serious implications in adult cardiology. Although left-sided CHD is known to be highly heritable, the underlying genetic determinants are largely unidentified. In this study, we sought to determine the impact of structural genomic variation on left-sided CHD and compared multiplex families (464 individuals with 174 affecteds (37.5%) in 59 multiplex families and 8 trios) to 1,582 well-phenotyped controls. 73 unique inherited or de novo CNVs in 54 individuals were identified in the left-sided CHD cohort. After stringent filtering, our gene inventory reveals 25 new candidates for LS-CHD pathogenesis, such as <em>SMC1A</em>, <em>MFAP4</em>, and <em>CTHRC1</em>, and overlaps with several known syndromic loci. Conservative estimation examining the overlap of the prioritized gene content with CNVs present only in affected individuals in our cohort implies a strong effect for unique CNVs in at least 10% of left-sided CHD cases. Enrichment testing of gene content in all identified CNVs showed a significant association with angiogenesis. In this first family-based CNV study of left-sided CHD, we found that both co-segregating and <em>de novo</em> events associate with disease in a complex fashion at structural genomic level. Often viewed as an anatomically circumscript disease, a subset of left-sided CHD may in fact reflect more general genetic perturbations of angiogenesis and/or vascular biology.</p> </div>", "links"=>[], "tags"=>["variants", "congenital", "left-sided"], "article_id"=>120517, "categories"=>["Genetics", "Medicine"], "users"=>["Marc-Phillip Hitz", "Louis-Philippe Lemieux-Perreault", "Christian Marshall", "Yassamin Feroz-Zada", "Robbie Davies", "Shi Wei Yang", "Anath Christopher Lionel", "Guylaine D'Amours", "Emmanuelle Lemyre", "Rebecca Cullum", "Jean-Luc Bigras", "Maryse Thibeault", "Philippe Chetaille", "Alexandre Montpetit", "Paul Khairy", "Bert Overduin", "Sabine Klaassen", "Pamela Hoodless", "Mona Nemer", "Alexandre F. R. Stewart", "Cornelius Boerkoel", "Stephen W. Scherer", "Andrea Richter", "Marie-Pierre Dubé", "Gregor Andelfinger"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002903.s001", "https://dx.doi.org/10.1371/journal.pgen.1002903.s002", "https://dx.doi.org/10.1371/journal.pgen.1002903.s003", "https://dx.doi.org/10.1371/journal.pgen.1002903.s004", "https://dx.doi.org/10.1371/journal.pgen.1002903.s005", "https://dx.doi.org/10.1371/journal.pgen.1002903.s006", "https://dx.doi.org/10.1371/journal.pgen.1002903.s007", "https://dx.doi.org/10.1371/journal.pgen.1002903.s008", "https://dx.doi.org/10.1371/journal.pgen.1002903.s009", "https://dx.doi.org/10.1371/journal.pgen.1002903.s010", "https://dx.doi.org/10.1371/journal.pgen.1002903.s011", "https://dx.doi.org/10.1371/journal.pgen.1002903.s012", "https://dx.doi.org/10.1371/journal.pgen.1002903.s013", "https://dx.doi.org/10.1371/journal.pgen.1002903.s014"], "stats"=>{"downloads"=>16, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Rare_Copy_Number_Variants_Contribute_to_Congenital_Left_Sided_Heart_Disease/120517", "title"=>"Rare Copy Number Variants Contribute to Congenital Left-Sided Heart Disease", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-06 00:08:37"}

PMC Usage Stats | Further Information

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F1000Prime