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2020-06-13

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cc-by (c) Torrico Avilés, Bàrbara et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/170559

Involvement of the 14-3-3 gene family in autism spectrum disorder and schizophrenia: Genetics, transcriptomics and functional analyses

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https://doi.org/10.3390/jcm9061851

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The 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.

Matèries

Autisme, Genètica humana, Esquizofrènia

Matèries (anglès)

Autism, Human genetics, Schizophrenia

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Articles publicats en revistes (Genètica, Microbiologia i Estadística)

Citació

TORRICO AVILÉS, Bàrbara, et al. Involvement of the 14-3-3 gene family in autism spectrum disorder and schizophrenia: Genetics, transcriptomics and functional analyses. Journal of Clinical Medicine. 2020. Vol. 9, num. 6, pags. 1851. ISSN 2077-0383. [consulted: 14 of August of 2026]. Available at: https://hdl.handle.net/2445/170559

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