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dc.contributor.authorBlake, J
dc.contributor.authorRiddell, A
dc.contributor.authorTheiss, S
dc.contributor.authorGonzalez, AP
dc.contributor.authorHaase, B
dc.contributor.authorJauch, A
dc.contributor.authorJanssen, JWG
dc.contributor.authorIbberson, D
dc.contributor.authorPavlinic, D
dc.contributor.authorMoog, U
dc.contributor.authorBenes, V
dc.contributor.authorRunz, H
dc.date.accessioned2021-02-05T01:12:06Z
dc.date.available2021-02-05T01:12:06Z
dc.date.issued2014-03-13
dc.identifierpii: PONE-D-13-44973
dc.identifier.citationBlake, J., Riddell, A., Theiss, S., Gonzalez, A. P., Haase, B., Jauch, A., Janssen, J. W. G., Ibberson, D., Pavlinic, D., Moog, U., Benes, V. & Runz, H. (2014). Sequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation. PLOS ONE, 9 (3), https://doi.org/10.1371/journal.pone.0090894.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/260305
dc.description.abstractBalanced chromosome abnormalities (BCAs) occur at a high frequency in healthy and diseased individuals, but cost-efficient strategies to identify BCAs and evaluate whether they contribute to a phenotype have not yet become widespread. Here we apply genome-wide mate-pair library sequencing to characterize structural variation in a patient with unclear neurodevelopmental disease (NDD) and complex de novo BCAs at the karyotype level. Nucleotide-level characterization of the clinically described BCA breakpoints revealed disruption of at least three NDD candidate genes (LINC00299, NUP205, PSMD14) that gave rise to abnormal mRNAs and could be assumed as disease-causing. However, unbiased genome-wide analysis of the sequencing data for cryptic structural variation was key to reveal an additional submicroscopic inversion that truncates the schizophrenia- and bipolar disorder-associated brain transcription factor ZNF804A as an equally likely NDD-driving gene. Deep sequencing of fluorescent-sorted wild-type and derivative chromosomes confirmed the clinically undetected BCA. Moreover, deep sequencing further validated a high accuracy of mate-pair library sequencing to detect structural variants larger than 10 kB, proposing that this approach is powerful for clinical-grade genome-wide structural variant detection. Our study supports previous evidence for a role of ZNF804A in NDD and highlights the need for a more comprehensive assessment of structural variation in karyotypically abnormal individuals and patients with neurocognitive disease to avoid diagnostic deception.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleSequencing of a Patient with Balanced Chromosome Abnormalities and Neurodevelopmental Disease Identifies Disruption of Multiple High Risk Loci by Structural Variation
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0090894
melbourne.affiliation.departmentMelbourne Dental School
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS One
melbourne.source.volume9
melbourne.source.issue3
dc.rights.licenseCC BY
melbourne.elementsid1102830
melbourne.contributor.authorGonzalez, Alexis Perez
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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