{"doi":"10.1371/journal.pgen.1007780","title":"Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization","abstract":null,"journal":"PLOS Genetics","year":2018,"id":636734,"datarank":0.5570358100056463,"base_score":3.713572066704308,"endowment":3.713572066704308,"self_citation_contribution":0.5570358100056463,"citation_network_contribution":0.0,"self_endowment_contribution":0.5570358100056463,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":497740,"name":"Jesper Eisfeldt","orcid":"0000-0003-3716-4917","position":1,"is_corresponding":false},{"id":497738,"name":"Maria Pettersson","orcid":"0000-0003-3120-1625","position":2,"is_corresponding":false},{"id":1652881,"name":"Johanna Lundin","orcid":null,"position":3,"is_corresponding":false},{"id":497745,"name":"Daniel Nilsson","orcid":"0000-0001-5831-385X","position":4,"is_corresponding":false},{"id":497739,"name":"Josephine Wincent","orcid":"0000-0002-1698-9605","position":5,"is_corresponding":false},{"id":1652882,"name":"Agne Lieden","orcid":null,"position":6,"is_corresponding":false},{"id":498511,"name":"Lovisa Lovmar","orcid":null,"position":7,"is_corresponding":false},{"id":498510,"name":"Jesper Ottosson","orcid":null,"position":8,"is_corresponding":false},{"id":497743,"name":"Jelena Gacic","orcid":"0000-0002-1431-7792","position":9,"is_corresponding":false},{"id":449956,"name":"Outi Mäkitie","orcid":"0000-0002-4547-001X","position":10,"is_corresponding":false},{"id":243301,"name":"Ann Nordgren","orcid":"0000-0003-3285-4281","position":11,"is_corresponding":false},{"id":1646326,"name":"Francesco Vezzi","orcid":"0000-0002-0243-0018","position":12,"is_corresponding":false},{"id":1529483,"name":"Valtteri Wirta","orcid":"0000-0003-3811-5439","position":13,"is_corresponding":false},{"id":34300,"name":"Max Käller","orcid":"0000-0001-6813-3051","position":14,"is_corresponding":false},{"id":812524,"name":"Tina Duelund Hjortshøj","orcid":"0000-0001-5201-2124","position":15,"is_corresponding":false},{"id":1652894,"name":"Cathrine Jespersgaard","orcid":null,"position":16,"is_corresponding":false},{"id":1652898,"name":"Rayan Houssari","orcid":null,"position":17,"is_corresponding":false},{"id":24528,"name":"Laura Pignata","orcid":"0000-0001-8835-5567","position":18,"is_corresponding":false},{"id":984705,"name":"Mads Bak","orcid":"0000-0003-2762-1002","position":19,"is_corresponding":false},{"id":1334218,"name":"Niels Tommerup","orcid":"0000-0003-2304-0112","position":20,"is_corresponding":false},{"id":497744,"name":"Elisabeth Syk Lundberg","orcid":"0000-0001-5692-725X","position":21,"is_corresponding":false},{"id":338862,"name":"Zeynep Tümer","orcid":"0000-0002-4777-5802","position":22,"is_corresponding":false},{"id":243300,"name":"Anna Lindstrand","orcid":"0000-0003-0806-5602","position":23,"is_corresponding":false},{"id":1652880,"name":"Lusine Nazaryan-Petersen","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization","abstract":"Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement. In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both \"simple\" and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements.","is_dataset_classified":null,"base_score":3.713572066704308,"endowment":3.713572066704308,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30419018","pmcid":"PMC6258378","openalex_id":"https://openalex.org/W2900783095","authors":[],"funders":[{"funder_name":"the Swedish Research Council","grant_id":"[2013-2603, 2017-02936]","title":null},{"funder_name":"the Marianne and Marcus Wallenberg foundation","grant_id":"[2014.0084]","title":null},{"funder_name":"the Danish Council for Independent Research - Medical Sciences","grant_id":"[4183-00482B]","title":null},{"funder_name":"Lundbeck Foundation","grant_id":"R151-2013-14290","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF17OC0027226","title":null},{"funder_name":"Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning","grant_id":"unidentified","title":"unidentified"},{"funder_name":"the Stockholm City Council","grant_id":"","title":null},{"funder_name":"the Erik Rönnberg Foundation and the Danish Council for Independent Research","grant_id":"","title":null},{"funder_name":"SciLifeLab national sequencing projects grant","grant_id":"","title":null},{"funder_name":"the Swedish Society for Medical Research big grant","grant_id":"","title":null},{"funder_name":"the Ulf Lundahl memory fund through the Swedish Brain Foundation","grant_id":"","title":null}],"total_grants":11,"fwci":3.8475,"citation_percentile":0.94091316,"influential_citations":0,"citation_trend":[{"year":2019,"count":12},{"year":2020,"count":9},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":6},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007780&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007780&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pgen.1007780","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pgen.1007780","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30419018","host_type":"repository"},{"url":"http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-153703","host_type":"repository"},{"url":"https://doaj.org/article/69ea9822f491409e90114bf9c70d2228","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6258378","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Replicative_and_non-replicative_mechanisms_in_the_formation_of_clustered_CNVs_are_indicated_by_whole_genome_characterization/7327742","host_type":"repository"},{"url":"http://hdl.handle.net/10138/288201","host_type":"journal"},{"url":"https://curis.ku.dk/portal/da/publications/replicative-and-nonreplicative-mechanisms-in-the-formation-of-clustered-cnvs-are-indicated-by-whole-genome-characterization(80559115-0b33-4147-b4b9-a80037de303b).html","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/80559115-0b33-4147-b4b9-a80037de303b","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6258378","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6258378?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pgen.1007780","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pgen.1007780","host_type":""},{"url":"https://curis.ku.dk/ws/files/217551931/journal.pgen.1007780.pdf","host_type":""},{"url":"https://hdl.handle.net/11591/486691","host_type":""},{"url":"https://publications.scilifelab.se/publication/51df1c5fe3f94631a980b3a69ab8490c","host_type":""},{"url":"https://doi.org/https://doi.org/10.1371/journal.pgen.1007780","host_type":""}],"fields_of_study":["Genomic variations and chromosomal abnormalities","Chromosomal and Genetic Variations","Prenatal Screening and Diagnostics","0301 basic medicine","03 medical and health sciences","0303 health sciences"],"mesh_terms":["Chromothripsis","Whole Genome Sequencing","DNA Replication","Humans","Gene Rearrangement","Genome, Human","Long Interspersed Nucleotide Elements","Alu Elements","Oligonucleotide Array Sequence Analysis","Chromosome Breakpoints","DNA Copy Number Variations"],"keywords":["Chromothripsis","Biology","Breakpoint","Chromosomal rearrangement","Genetics","Copy-number variation","Genome","Gene duplication","Gene rearrangement","Whole genome sequencing","Chromosome","Chromosomal translocation","Computational biology","Karyotype","Gene","DNA","Genome instability","DNA Replication","DNA Copy Number Variations","DISORDERS","VARIANTS","QH426-470","Medical Genetics and Genomics","Chromosome Breakpoints","Alu Elements","Humans","Oligonucleotide Array Sequence Analysis","REPAIR","CONSEQUENCES","Genome, Human","REARRANGEMENTS","DNA BREAKS","Medicinsk genetik och genomik","DIVERSE","STRUCTURAL VARIATION","ALIGNMENT","Biomedicine","Long Interspersed Nucleotide Elements","Genetics, developmental biology, physiology","Research Article"],"sdg_mappings":[{"sdg_number":13,"sdg_label":"13. 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