{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:32:50Z","timestamp":1787941970412,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (<jats:italic>n<\/jats:italic>\u00a0=\u00a0519).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in <jats:italic>OPTN<\/jats:italic> in an Alzheimer's disease participant; (2) a duplication of exons 1\u20135 in <jats:italic>PARK7<\/jats:italic> in an amyotrophic lateral sclerosis participant; (3) a duplication of &gt;3\u00a0Mb, which encompassed <jats:italic>ABCC6<\/jats:italic>, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7\u201311 in <jats:italic>SAMHD1<\/jats:italic> in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1986","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T06:33:32Z","timestamp":1654324412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeted copy number variant identification across the neurodegenerative disease spectrum"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-9304","authenticated-orcid":false,"given":"Allison A.","family":"Dilliott","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery Montreal Neurological Institute and Hospital McGill University  Montr\u00e9al Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina K.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Robarts Research Institute Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agessandro","family":"Abrahao","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine Sunnybrook Health Sciences Centre University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm A.","family":"Binns","sequence":"additional","affiliation":[{"name":"Rotman Research Institute Baycrest Health Sciences  Toronto Ontario Canada"},{"name":"Dalla Lana School of Public Health University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"Black","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine Sunnybrook Health Sciences Centre University of Toronto  Toronto Ontario Canada"},{"name":"LCCampbell Cognitive Neurology Research Unit Hurvitz Brain Sciences Research Program Sunnybrook Health Sciences Research Program Sunnybrook Health Sciences Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Borrie","sequence":"additional","affiliation":[{"name":"St. Joseph\u2019s Health Care Centre  London Ontario Canada"},{"name":"Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dar","family":"Dowlatshahi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Finger","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurological Sciences Schulich School of Medicine and Dentistry Western University  London Ontario Canada"},{"name":"Lawson Health Research Institute  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne E.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Keenan Research Centre for Biomedical Science Li Ka Shing Knowledge Institute St. Michael's Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"Bruy\u00e8re Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morris","family":"Freedman","sequence":"additional","affiliation":[{"name":"Rotman Research Institute Baycrest Health Sciences  Toronto Ontario Canada"},{"name":"Division of Neurology Department of Medicine Baycrest Health Sciences Mt. 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Safra Program in Parkinson\u2019s Disease and the Morton and Gloria Shulman Movement Disorders Clinic Toronto Western Hospital  Toronto Ontario Canada"},{"name":"Department of Medicine Division of Neurology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Mandzia","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurological Sciences Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Masellis","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Neurology University of Toronto  Toronto Ontario Canada"},{"name":"Cognitive &amp; Movement Disorders Clinic L.C. Campbell Cognitive Neurology Research Unit Hurvitz Brain ScienceProgram Sunnybrook Health Sciences Centre  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen H.","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Robarts Research Institute Schulich School of Medicine and Dentistry Western University  London Ontario Canada"},{"name":"Department of Clinical Neurological Sciences Schulich School of Medicine and Dentistry Western University  London Ontario Canada"},{"name":"Cognitive Neurology and Alzheimer\u2019s Disease Research Centre Parkwood Institute St. Joseph\u2019s Health Care  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce G.","family":"Pollock","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health  Toronto Ontario Canada"},{"name":"Department of Psychiatry Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek K.","family":"Rajji","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health  Toronto Ontario Canada"},{"name":"Department of Psychiatry and Toronto Dementia Research Alliance University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Rogaeva","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrios J.","family":"Sahlas","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Saposnik","sequence":"additional","affiliation":[{"name":"Li Ka Shing Knowledge Institute St. Michael\u2019s Hospital  Toronto Ontario Canada"},{"name":"Clinical Outcomes and Decision Neuroscience Unit St. Michael\u2019s Hospital University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sato","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dallas","family":"Seitz","sequence":"additional","affiliation":[{"name":"Cumming School of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christen","family":"Shoesmith","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D. L.","family":"Steeves","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurological Sciences Schulich School of Medicine and Dentistry Western University  London Ontario Canada"},{"name":"Division of Neurology St. Michael\u2019s Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Swartz","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine Sunnybrook Health Sciences Centre University of Toronto  Toronto Ontario Canada"},{"name":"LCCampbell Cognitive Neurology Research Unit Hurvitz Brain Sciences Research Program Sunnybrook Health Sciences Research Program Sunnybrook Health Sciences Centre  Toronto Ontario Canada"},{"name":"Department of Medicine Division of Neurology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Tan","sequence":"additional","affiliation":[{"name":"Rotman Research Institute Baycrest Health Sciences  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Tang\u2010Wai","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Neurology University of Toronto  Toronto Ontario Canada"},{"name":"Krembil Research Institute Toronto Western Hospital  Toronto Ontario Canada"},{"name":"University Health Network Memory Clinic Toronto Western Hospital  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Diseases University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Turnbull","sequence":"additional","affiliation":[{"name":"Department of Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne","family":"Zinman","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Medicine Sunnybrook Health Sciences Centre University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ONDRI Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":false,"given":"Robert A.","family":"Hegele","sequence":"additional","affiliation":[{"name":"Robarts Research Institute Schulich School of Medicine and Dentistry Western University  London Ontario Canada"},{"name":"Department of Biochemistry Schulich School of Medicine and Dentistry Western University  London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20666"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.11.018"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/76109"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010003\u20100108\u20100"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.01.012"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD\u2010160469"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3791\/57266"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2016.415"},{"key":"e_1_2_11_10_1","first-page":"1","article-title":"The ONDRISeq panel: Custom\u2010designed next\u2010generation sequencing of genes related to neurodegeneration","volume":"16032","author":"Farhan S. 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