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dc.contributor.authorTorrico, Bàrbara
dc.contributor.authorAntón-Galindo, Ester
dc.contributor.authorFernàndez-Castillo, Noèlia
dc.contributor.authorRojo-Francàs, Eva
dc.contributor.authorGhorbani, Sadaf
dc.contributor.authorPineda-Cirera, Laura
dc.contributor.authorHervas, Amaia
dc.contributor.authorRueda, Isabel
dc.contributor.authorMoreno, Estefanía
dc.contributor.authorFullerton, Janice M.
dc.contributor.authorCasadó, Vicent
dc.contributor.authorBuitelaar, Jan K
dc.contributor.authorRommelse, Nanda
dc.contributor.authorFranke, Barbara
dc.contributor.authorReif, Andreas
dc.contributor.authorChiocchetti, Andreas G
dc.contributor.authorFreitag, Christine
dc.contributor.authorKleppe, Rune
dc.contributor.authorHaavik, Jan
dc.contributor.authorToma, Claudio
dc.contributor.authorCormand, Bru
dc.date.accessioned2021-06-14T13:00:02Z
dc.date.available2021-06-14T13:00:02Z
dc.date.created2021-02-12T13:30:16Z
dc.date.issued2020
dc.identifier.issn2077-0383
dc.identifier.urihttps://hdl.handle.net/11250/2759346
dc.description.abstractThe 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (c.659-660insT, p.L220Ffs*18). Here, we explored the contribution of the seven human 14-3-3 family members in ASD and other psychiatric disorders by investigating the: (i) functional impact of the 14-3-3ζ mutation p.L220Ffs*18 by assessing solubility, target binding and dimerization; (ii) contribution of common risk variants in 14-3-3 genes to ASD and additional psychiatric disorders; (iii) burden of rare variants in ASD and schizophrenia; and iv) 14-3-3 gene expression using ASD and schizophrenia transcriptomic data. We found that the mutant 14-3-3ζ protein had decreased solubility and lost its ability to form heterodimers and bind to its target tyrosine hydroxylase. Gene-based analyses using publicly available datasets revealed that common variants in YWHAE contribute to schizophrenia (p = 6.6 × 10−7), whereas ultra-rare variants were found enriched in ASD across the 14-3-3 genes (p = 0.017) and in schizophrenia for YWHAZ (meta-p = 0.017). Furthermore, expression of 14-3-3 genes was altered in post-mortem brains of ASD and schizophrenia patients. Our study supports a role for the 14-3-3 family in ASD and schizophrenia.en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleInvolvement of the 14-3-3 Gene Family in Autism Spectrum Disorder and Schizophrenia: Genetics, Transcriptomics and Functional Analysesen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2020 by the authorsen_US
dc.source.articlenumber1851en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/jcm9061851
dc.identifier.cristin1889199
dc.source.journalJournal of Clinical Medicineen_US
dc.relation.projectEC/H2020/643051en_US
dc.relation.projectEC/H2020/667302en_US
dc.identifier.citationJournal of Clinical Medicine. 2020, 9 (6), 1851.en_US
dc.source.volume9en_US
dc.source.issue6en_US


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