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Although our understanding of the genetic foundations of PD has advanced, a substantial portion of the genetic variation contributing to disease risk remains unknown. Current PD genetic studies have primarily focused on one form of genetic variation, single nucleotide variants (SNVs), while other important forms of genetic variation, such as structural variants (SVs), are mostly ignored due to the complexity of detecting these variants with traditional sequencing methods. Yet, these forms of genetic variation play crucial roles in gene expression and regulation in the human brain and are causative of numerous neurological disorders, including forms of PD. This review aims to provide a comprehensive overview of our current understanding of the involvement of coding and noncoding SVs in the genetic architecture of PD.<\/jats:p>","DOI":"10.3390\/ijms25094801","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T08:02:22Z","timestamp":1714723342000},"page":"4801","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of Structural Variants in the Genetic Architecture of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-4698","authenticated-orcid":false,"given":"Abigail","family":"Miano-Burkhardt","sequence":"first","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA"},{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Alvarez Jerez","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9177-9587","authenticated-orcid":false,"given":"Kensuke","family":"Daida","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA"},{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bandres Ciga","sequence":"additional","affiliation":[{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8003-4029","authenticated-orcid":false,"given":"Kimberley J.","family":"Billingsley","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA"},{"name":"Center for Alzheimer\u2019s and Related Dementias, National Institute on Aging, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson Pandemic-A Call to Action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S1474-4422(19)30287-X","article-title":"The genetic architecture of Parkinson\u2019s disease","volume":"19","author":"Blauwendraat","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/ng.3955","article-title":"A meta-analysis of genome-wide association studies identifies 17 new Parkinson\u2019s disease risk loci","volume":"49","author":"Chang","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/ng.3043","article-title":"Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson\u2019s disease","volume":"46","author":"Nalls","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41588-023-01584-8","article-title":"Multi-ancestry genome-wide association meta-analysis of Parkinson\u2019s disease","volume":"56","author":"Kim","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","article-title":"Identification of Novel Risk Loci, Causal Insights, and Heritable Risk for Parkinson\u2019s Disease: A Meta-Analysis of Genome-Wide Association Studies","volume":"18","author":"Nalls","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nature09792","article-title":"Initial impact of the sequencing of the human genome","volume":"470","author":"Lander","year":"2011","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pang, A.W., MacDonald, J.R., Pinto, D., Wei, J., Rafiq, M.A., Conrad, D.F., Park, H., Hurles, M.E., Lee, C., and Venter, J.C. (2010). Towards a comprehensive structural variation map of an individual human genome. Genome Biol., 11.","DOI":"10.1186\/gb-2010-11-5-r52"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41576-018-0003-4","article-title":"Piercing the dark matter: Bioinformatics of long-range sequencing and mapping","volume":"19","author":"Sedlazeck","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature15394","article-title":"An Integrated Map of Structural Variation in 2504 Human Genomes","volume":"526","author":"Sudmant","year":"2015","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1038\/s41467-020-16736-1","article-title":"Functional annotation of rare structural variation in the human brain","volume":"11","author":"Han","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/ana.26608","article-title":"Genome-Wide Analysis of Structural Variants in Parkinson Disease","volume":"93","author":"Billingsley","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100316","DOI":"10.1016\/j.xgen.2023.100316","article-title":"Genome-wide structural variant analysis identifies risk loci for non-Alzheimer\u2019s dementias","volume":"3","author":"Kaivola","year":"2023","journal-title":"Cell Genom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/s41586-019-1913-9","article-title":"Patterns of somatic structural variation in human cancer genomes","volume":"578","author":"Li","year":"2020","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/dgd.12608","article-title":"Nanopore sequencing: Review of potential applications in functional genomics","volume":"61","author":"Kono","year":"2019","journal-title":"Dev. Growth Differ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41593-022-01031-7","article-title":"Integrating whole-genome sequencing with multi-omic data reveals the impact of structural variants on gene regulation in the human brain","volume":"25","author":"Vialle","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1038\/s41380-023-01978-4","article-title":"The contribution of copy number variants to psychiatric symptoms and cognitive ability","volume":"28","author":"Mollon","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1136\/jmg.40.8.575","article-title":"Molecular Characterisation of the 22q13 Deletion Syndrome Supports the Role of Haploinsufficiency of SHANK3\/PROSAP2 in the Major Neurological Symptoms","volume":"40","author":"Wilson","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_19","unstructured":"Van Esch, H. (2020). GeneReviews\u00ae [Internet], University of Washington."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/jmedgenet-2015-103387","article-title":"The importance of genetic diagnosis for Duchenne muscular dystrophy","volume":"53","author":"Ginjaar","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1093\/brain\/awab386","article-title":"Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia","volume":"145","author":"Banneau","year":"2022","journal-title":"Brain"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yoon, J., and Mao, Y. (2021). Dissecting Molecular Genetic Mechanisms of 1q21.1 CNV in Neuropsychiatric Disorders. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115811"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"300","DOI":"10.5603\/PJNNS.a2021.0038","article-title":"Movement disorders associated with chromosomal aberrations diagnosed in adult patients","volume":"55","author":"Figura","year":"2021","journal-title":"Neurol. Neurochir. Pol."},{"key":"ref_24","first-page":"137","article-title":"Torsion Dystonia in Panay, Philippines","volume":"14","author":"Lee","year":"1976","journal-title":"Adv. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/ejhg.2014.292","article-title":"New insights into the genetics of X-linked dystonia-parkinsonism (XDP, DYT3)","volume":"23","author":"Domingo","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1086\/512129","article-title":"Reduced Neuron-Specific Expression of the TAF1 Gene Is Associated with X-Linked Dystonia-Parkinsonism","volume":"80","author":"Makino","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10347","DOI":"10.1073\/pnas.1831949100","article-title":"Specific sequence changes in multiple transcript system DYT3 are associated with X-linked dystonia parkinsonism","volume":"100","author":"Nolte","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.cell.2018.02.011","article-title":"Dissecting the Causal Mechanism of X-Linked Dystonia-Parkinsonism by Integrating Genome and Transcriptome Assembly","volume":"172","author":"Aneichyk","year":"2018","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1002\/mds.27441","article-title":"Genome Editing in Induced Pluripotent Stem Cells Rescues TAF1 Levels in X-Linked Dystonia-Parkinsonism","volume":"33","author":"Rakovic","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_30","first-page":"438","article-title":"Structural genomic variations and Parkinson\u2019s disease","volume":"108","author":"Ruz","year":"2017","journal-title":"Minerva Medica"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3389\/fneur.2018.01021","article-title":"SNCA Multiplication Investigators of the GEoPD Consortium A Meta-Analysis of \u03b1-Synuclein Multiplication in Familial Parkinsonism","volume":"9","author":"Book","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The Human Genome Browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the \u03b1-Synuclein Gene Identified in Families with Parkinson\u2019s Disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/mds.25421","article-title":"Alpha-Synuclein p.H50Q, a Novel Pathogenic Mutation for Parkinson\u2019s Disease","volume":"28","author":"Encarnacion","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ng0298-106","article-title":"AlaSOPro Mutation in the Gene Encoding \u03b1-Synuclein in Parkinson\u2019s Disease","volume":"18","author":"Kuhn","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/ana.23894","article-title":"G51D \u03b1-Synuclein Mutation Causes a Novel Parkinsonian-Pyramidal Syndrome","volume":"73","author":"Lesage","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/ana.10795","article-title":"The New Mutation, E46K, of \u03b1-Synuclein Causes Parkinson and Lewy Body Dementia","volume":"55","author":"Zarranz","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1090278","article-title":"\u03b1-Synuclein Locus Triplication Causes Parkinson\u2019s Disease","volume":"302","author":"Singleton","year":"2003","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1212\/01.wnl.0000271080.53272.c7","article-title":"\u03b1-Synuclein Gene Duplication Is Present in Sporadic Parkinson Disease","volume":"70","author":"Ahn","year":"2008","journal-title":"Neurology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/ana.10846","article-title":"Comparison of Kindreds with Parkinsonism and \u03b1-Synuclein Genomic Multiplications","volume":"55","author":"Farrer","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_41","first-page":"546462","article-title":"Four Copies of SNCA Responsible for Autosomal Dominant Parkinson\u2019s Disease in Two Italian Siblings","volume":"2015","author":"Ferese","year":"2015","journal-title":"Parkinson\u2019s Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1212\/01.wnl.0000254458.17630.c5","article-title":"Phenotypic variation in a large Swedish pedigree due to SNCA duplication and triplication","volume":"68","author":"Fuchs","year":"2007","journal-title":"Neurology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10048-009-0229-6","article-title":"Analysis of exon dosage using MLPA in South African Parkinson\u2019s disease patients","volume":"11","author":"Keyser","year":"2009","journal-title":"Neurogenetics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/ana.20753","article-title":"Clinical Heterogeneity of \u03b1-Synuclein Gene Duplication in Parkinson\u2019s Disease","volume":"59","author":"Nishioka","year":"2006","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.parkreldis.2015.06.005","article-title":"Early-onset parkinsonism caused by alpha-synuclein gene triplication: Clinical and genetic findings in a novel family","volume":"21","author":"Olgiati","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1002\/mds.23313","article-title":"Clinical course of the first Asian family with Parkinsonism related to SNCA triplication","volume":"25","author":"Sekine","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1001\/archneurol.2008.555","article-title":"\u03b1-Synuclein Gene Rearrangements in Dominantly Inherited Parkinsonism: Frequency, Phenotype, and Mechanisms","volume":"66","author":"Lesage","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/ncomms1453","article-title":"Parkinson\u2019s disease induced pluripotent stem cells with triplication of the \u03b1-synuclein locus","volume":"2","author":"Devine","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1212\/01.WNL.0000127517.33208.F4","article-title":"\u03b1-Synuclein in Blood and Brain from Familial Parkinson Disease with SNCA Locus Triplication","volume":"62","author":"Miller","year":"2004","journal-title":"Neurology"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Byers, B., Cord, B., Nguyen, H.N., Sch\u00fcle, B., Fenno, L., Lee, P.C., Deisseroth, K., Langston, J.W., Pera, R.R., and Palmer, T.D. (2011). SNCA Triplication Parkinson\u2019s Patient\u2019s iPSC-Derived DA Neurons Accumulate \u03b1-Synuclein and Are Susceptible to Oxidative Stress. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026159"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/s41419-022-05330-6","article-title":"Modeling native and seeded Synuclein aggregation and related cellular dysfunctions in dopaminergic neurons derived by a new set of isogenic iPSC lines with SNCA multiplications","volume":"13","author":"Iannielli","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1126\/science.aam9080","article-title":"Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson\u2019s disease","volume":"357","author":"Burbulla","year":"2017","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e1994","DOI":"10.1038\/cddis.2015.318","article-title":"Elevated \u03b1-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson\u2019s patient-derived induced pluripotent stem cells","volume":"6","author":"Oliveira","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.parkreldis.2015.09.007","article-title":"Autosomal dominant Parkinson\u2019s disease caused by SNCA duplications","volume":"22","author":"Konno","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/33416","article-title":"Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism","volume":"392","author":"Kitada","year":"1998","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/ane.12563","article-title":"The genetic background of Parkinson\u2019s disease: Current progress and future prospects","volume":"134","author":"Kalinderi","year":"2016","journal-title":"Acta Neurol. Scand."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Gr\u00fcnewald, A., Voges, L., Rakovic, A., Kasten, M., Vandebona, H., Hemmelmann, C., Lohmann, K., Orolicki, S., Ramirez, A., and Schapira, A.H.V. (2010). Mutant Parkin Impairs Mitochondrial Function and Morphology in Human Fibroblasts. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0012962"},{"key":"ref_58","first-page":"544","article-title":"Mitochondrial complex I and IV activities in leukocytes from patients with parkin mutations","volume":"19","author":"Elibol","year":"2003","journal-title":"Mov. Disord."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"43628","DOI":"10.1074\/jbc.M308947200","article-title":"Parkin-Deficient Mice Exhibit Nigrostriatal Deficits but Not Loss of Dopaminergic Neurons","volume":"278","author":"Goldberg","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1093\/hmg\/ddg239","article-title":"Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse","volume":"12","author":"Itier","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"18614","DOI":"10.1074\/jbc.M401135200","article-title":"Mitochondrial Dysfunction and Oxidative Damage in Parkin-Deficient Mice","volume":"279","author":"Palacino","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/1531-8257(200009)15:5<884::AID-MDS1019>3.0.CO;2-8","article-title":"An Autopsy Case of Autosomal-Recessive Juvenile Parkinsonism with a Homozygous Exon 4 Deletion in the Parkin Gene","volume":"15","author":"Hayashi","year":"2000","journal-title":"Mov. Disord."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/mds.25346","article-title":"Lewy Body Pathology in a Patient with a Homozygous Parkin Deletion","volume":"28","author":"Miyakawa","year":"2013","journal-title":"Mov. Disord."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1212\/WNL.51.3.890","article-title":"Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q","volume":"51","author":"Mori","year":"1998","journal-title":"Neurology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1212\/01.WNL.0000134657.25904.0B","article-title":"Parkin-Positive Autosomal Recessive Juvenile Parkinsonism with \u03b1-Synuclein-Positive Inclusions","volume":"63","author":"Sasaki","year":"2004","journal-title":"Neurology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1353-8020(98)00015-7","article-title":"Clinical, pathologic and genetic studies on autosomal recessive early-onset parkinsonism with diurnal fluctuation","volume":"4","author":"Yamamura","year":"1998","journal-title":"Park. Relat. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ahmad, A., Nkosi, D., and Iqbal, M.A. (2023). PARK2 Microdeletion or Duplications Have Been Implicated in Different Neurological Disorders Including Early Onset Parkinson Disease. Genes, 14.","DOI":"10.3390\/genes14030600"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/mp.2012.161","article-title":"Genome-Wide Analysis of Rare Copy Number Variations Reveals PARK2 as a Candidate Gene for Attention-Deficit\/hyperactivity Disorder","volume":"19","author":"Jarick","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00109-013-1107-0","article-title":"An Emerging Role of PARK2 in Cancer","volume":"92","author":"Xu","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nature07953","article-title":"Autism genome-wide copy number variation reveals ubiquitin and neuronal genes","volume":"459","author":"Glessner","year":"2009","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13229-016-0087-7","article-title":"Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder","volume":"7","author":"Yin","year":"2016","journal-title":"Mol. Autism"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/ana.25787","article-title":"Characterization of Recessive Parkinson Disease in a Large Multicenter Study","volume":"88","author":"Lesage","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/mds.27352","article-title":"Genotype-Phenotype Relations for the Parkinson\u2019s Disease Genes Parkin, PINK1, DJ1: MDSGene Systematic Review","volume":"33","author":"Kasten","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/gcc.10236","article-title":"Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer","volume":"38","author":"Denison","year":"2003","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1002\/mds.25132","article-title":"Systematic Review and UK-Based Study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in Early-Onset Parkinson\u2019s Disease","volume":"27","author":"Kilarski","year":"2012","journal-title":"Mov. Disord."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1093\/brain\/awab456","article-title":"Heterozygous PRKN Mutations Are Common but Do Not Increase the Risk of Parkinson\u2019s Disease","volume":"145","author":"Zhu","year":"2022","journal-title":"Brain"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1212\/WNL.0b013e3181f4d832","article-title":"A Comprehensive Analysis of Deletions, Multiplications, and Copy Number Variations in PARK2","volume":"75","author":"Kay","year":"2010","journal-title":"Neurology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5637","DOI":"10.1093\/hmg\/ddv277","article-title":"Heterozygote carriers for CNVs in PARK2 are at increased risk of Parkinson\u2019s disease","volume":"24","author":"Huttenlocher","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Daida, K., Funayama, M., Billingsley, K.J., Malik, L., Miano-Burkhardt, A., Leonard, H.L., Makarious, M.B., Iwaki, H., Ding, J., and Gibbs, J.R. (2023). Long-Read Sequencing Resolves a Complex Structural Variant in PRKN Parkinson\u2019s Disease. medRxiv.","DOI":"10.1101\/2023.08.14.23293948"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.1077209","article-title":"Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism","volume":"299","author":"Bonifati","year":"2003","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/ana.10675","article-title":"The Role of Pathogenic DJ-1 Mutations in Parkinson\u2019s Disease","volume":"54","author":"Healy","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/mds.20131","article-title":"Analysis of an Early-Onset Parkinson\u2019s Disease Cohort for DJ-1 Mutations","volume":"19","author":"Clark","year":"2004","journal-title":"Mov. Disord."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.neulet.2013.07.013","article-title":"Detection of copy number changes in genes associated with Parkinson\u2019s disease in Iranian patients","volume":"551","author":"Darvish","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1002\/mds.28812","article-title":"Early-Onset Parkinson\u2019s Disease: A Novel Deletion Comprising the DJ-1 and TNFRSF9 Genes","volume":"36","author":"Haerle","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"100020","DOI":"10.1016\/j.dscb.2021.100020","article-title":"DJ-1 and Parkinson\u2019s Disease","volume":"3","author":"Ross","year":"2021","journal-title":"Brain Disord. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1126\/science.1096284","article-title":"Hereditary Early-Onset Parkinson\u2019s Disease Caused by Mutations in PINK1","volume":"304","author":"Valente","year":"2004","journal-title":"Science"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1002\/humu.21277","article-title":"Genetic Etiology of Parkinson Disease Associated with Mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 Genes: A Mutation Update","volume":"31","author":"Nuytemans","year":"2010","journal-title":"Hum. Mutat."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1212\/01.WNL.0000164009.36740.4E","article-title":"Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism","volume":"64","author":"Li","year":"2005","journal-title":"Neurology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1002\/humu.9472","article-title":"Whole gene deletion and splicing mutations expand thePINK1 genotypic spectrum","volume":"28","author":"Marongiu","year":"2006","journal-title":"Hum. Mutat."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s10048-009-0174-4","article-title":"A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson\u2019s disease","volume":"10","author":"Cazeneuve","year":"2009","journal-title":"Neurogenetics"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Vizziello, M., Borellini, L., Franco, G., and Ardolino, G. (2021). Disruption of Mitochondrial Homeostasis: The Role of PINK1 in Parkinson\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10113022"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13024-019-0321-9","article-title":"A CRISPR monkey model unravels a unique function of PINK1 in primate brains","volume":"14","author":"Yang","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/s41422-019-0142-y","article-title":"CRISPR\/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys","volume":"29","author":"Yang","year":"2019","journal-title":"Cell Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1542\/peds.112.1.101","article-title":"A Population-Based Study of the 22q11.2 Deletion: Phenotype, Incidence, and Contribution to Major Birth Defects in the Population","volume":"112","author":"Botto","year":"2003","journal-title":"Pediatrics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1136\/jmg.35.9.789-a","article-title":"The annual incidence of DiGeorge\/velocardiofacial syndrome","volume":"35","author":"Devriendt","year":"1998","journal-title":"J. Med. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1136\/adc.79.4.348","article-title":"A population study of chromosome 22q11 deletions in infancy","volume":"79","author":"Goodship","year":"1998","journal-title":"Arch. Dis. Child."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1093\/hmg\/9.16.2421","article-title":"The 22q11 Deletion Syndromes","volume":"9","author":"Scambler","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_98","first-page":"123","article-title":"22q11 Deletion Syndrome: Current Perspective","volume":"8","author":"Delil","year":"2015","journal-title":"Appl. Clin. Genet."},{"key":"ref_99","unstructured":"McDonald-McGinn, D.M. (2022). The Chromosome 22q11.2 Deletion Syndrome: A Multidisciplinary Approach to Diagnosis and Treatment, Academic Press."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.parkreldis.2014.06.020","article-title":"Chromosome 22q11.2 Deletion May Contain a Locus for Recessive Early-Onset Parkinson\u2019s Disease","volume":"20","author":"Ogaki","year":"2014","journal-title":"Park. Relat. Disord."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1001\/jamaneurol.2013.3646","article-title":"Association between Early-Onset Parkinson Disease and 22q11.2 Deletion Syndrome: Identification of a Novel Genetic Form of Parkinson Disease and Its Clinical Implications","volume":"70","author":"Butcher","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S1474-4422(16)00071-5","article-title":"Deletions at 22q11.2 in Idiopathic Parkinson\u2019s Disease: A Combined Analysis of Genome-Wide Association Data","volume":"15","author":"Mok","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41525-021-00267-9","article-title":"Structural variation analysis of 6500 whole genome sequences in amyotrophic lateral sclerosis","volume":"7","author":"Iacoangeli","year":"2022","journal-title":"npj Genom. Med."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wang, H., Dombroski, B.A., Cheng, P.L., Tucci, A., Si, Y.Q., Farrell, J.J., Tzeng, J.-Y., Leung, Y.Y., Malamon, J.S., and Wang, L.-S. (2023). Structural Variation Detection and Association Analysis of Whole-Genome-Sequence Data from 16,905 Alzheimer\u2019s Diseases Sequencing Project Subjects. medRxiv.","DOI":"10.1101\/2023.09.13.23295505"},{"key":"ref_105","unstructured":"(2024, January 21). GitHub-Broadinstitute\/gatk-Sv: A Structural Variation Pipeline for Short-Read Sequencing. n.d. GitHub. Available online: https:\/\/github.com\/broadinstitute\/gatk-sv."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/s41586-020-2287-8","article-title":"A structural variation reference for medical and population genetics","volume":"581","author":"Collins","year":"2020","journal-title":"Nature"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.ajhg.2021.03.014","article-title":"Expectations and blind spots for structural variation detection from long-read assemblies and short-read genome sequencing technologies","volume":"108","author":"Zhao","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Leonard, H., Jonson, C., Levine, K., Lake, J., Hertslet, L., Jones, L., Patel, D., Kim, J., Bandres-Ciga, S., and Terry, N. (2024). Assessing the Lack of Diversity in Genetics Research across Neurodegenerative Diseases: A Systematic Review of the GWAS Catalog and Literature. medRxiv.","DOI":"10.1101\/2024.01.08.24301007"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Mahmoud, M., Huang, Y., Garimella, K., Audano, P.A., Wan, W., Prasad, N., Handsaker, R.E., Hall, S., Pionzio, A., and Schatz, M.C. (2023). Utility of Long-Read Sequencing for All of Us. bioRxiv.","DOI":"10.1101\/2023.01.23.525236"},{"key":"ref_110","unstructured":"(2024, February 04). Long-Read Sequencing. n.d, Available online: https:\/\/card.nih.gov\/research-programs\/long-read-sequencing."},{"key":"ref_111","unstructured":"(2024, January 21). Website. n.d. Available online: https:\/\/www.genomeweb.com\/sequencing\/nih-study-demonstrates-nanopore-sequencing-population-scale-genomics."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Global Parkinson\u2019s Genetics Program (2021). GP2: The Global Parkinson\u2019s Genetics Program. Mov. Disord., 36, 842\u2013851.","DOI":"10.1002\/mds.28494"},{"key":"ref_113","unstructured":"Blythe, L. (2023, December 22). 2020. Understanding the Genetic Architecture of Parkinson\u2019s Disease. GP2. Available online: https:\/\/gp2.org\/."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1093\/brain\/awy157","article-title":"Somatic copy number gains of \u03b1-synuclein (SNCA) in Parkinson\u2019s disease and multiple system atrophy brains","volume":"141","author":"Mokretar","year":"2018","journal-title":"Brain"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s40478-019-0873-5","article-title":"Investigation of somatic CNVs in brains of synucleinopathy cases using targeted SNCA analysis and single cell sequencing","volume":"7","author":"Kalyva","year":"2019","journal-title":"Acta Neuropathol. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4801\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:34:57Z","timestamp":1760106897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/9\/4801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,27]]},"references-count":115,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25094801"],"URL":"https:\/\/doi.org\/10.3390\/ijms25094801","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,27]]}}}