Welcome to the UPF Digital Repository

Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.

Show simple item record

dc.contributor.author Codina i Solà, Marta, 1988-
dc.contributor.author Rodríguez Santiago, Benjamín
dc.contributor.author Homs Raubert, Aïda, 1983-
dc.contributor.author Santoyo-Lopez, Javier
dc.contributor.author Rigau, Maria
dc.contributor.author Aznar Laín, Gemma
dc.contributor.author Campo Casanelles, Miguel del, 1966-
dc.contributor.author Gener, Blanca
dc.contributor.author Gabau, Elisabeth
dc.contributor.author Botella, María Pilar
dc.contributor.author Gutiérrez Arumi, Armand, 1980-
dc.contributor.author Antiñolo, Guillermo
dc.contributor.author Pérez Jurado, Luis Alberto
dc.contributor.author Cuscó Martí, Ivon, 1973-
dc.date.accessioned 2015-06-05T06:58:35Z
dc.date.available 2015-06-05T06:58:35Z
dc.date.issued 2015
dc.identifier.citation Codina-Solà M, Rodríguez-Santiago B, Homs A, Santoyo J, Rigau M, Aznar-Laín G. et al. Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders. Mol Autism. 2015 Apr 15;6:21. DOI: 10.1186/s13229-015-0017-0.
dc.identifier.issn 2040-2392
dc.identifier.uri http://hdl.handle.net/10230/23736
dc.description.abstract BACKGROUND: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with high heritability. Recent findings support a highly heterogeneous and complex genetic etiology including rare de novo and inherited mutations or chromosomal rearrangements as well as double or multiple hits. METHODS: We performed whole-exome sequencing (WES) and blood cell transcriptome by RNAseq in a subset of male patients with idiopathic ASD (n = 36) in order to identify causative genes, transcriptomic alterations, and susceptibility variants. RESULTS: We detected likely monogenic causes in seven cases: five de novo (SCN2A, MED13L, KCNV1, CUL3, and PTEN) and two inherited X-linked variants (MAOA and CDKL5). Transcriptomic analyses allowed the identification of intronic causative mutations missed by the usual filtering of WES and revealed functional consequences of some rare mutations. These included aberrant transcripts (PTEN, POLR3C), deregulated expression in 1.7% of mutated genes (that is, SEMA6B, MECP2, ANK3, CREBBP), allele-specific expression (FUS, MTOR, TAF1C), and non-sense-mediated decay (RIT1, ALG9). The analysis of rare inherited variants showed enrichment in relevant pathways such as the PI3K-Akt signaling and the axon guidance. CONCLUSIONS: Integrative analysis of WES and blood RNAseq data has proven to be an efficient strategy to identify likely monogenic forms of ASD (19% in our cohort), as well as additional rare inherited mutations that can contribute to ASD risk in a multifactorial manner. Blood transcriptomic data, besides validating 88% of expressed variants, allowed the identification of missed intronic mutations and revealed functional correlations of genetic variants, including changes in splicing, expression levels, and allelic expression.
dc.description.sponsorship This work was funded by grants from the Spanish Ministry of Health (FIS PI1002512, PI1302481, and PI1300823 cofunded by FEDER), Fundación Alicia Koplowitz and Generalitat de Catalunya (2014SGR1468). The ‘Medical Genome Project’ is a joint initiative of the Consejería de Salud de la Junta de Andalucía and Roche, supported by the ‘Programa Nacional de Proyectos de investigación Aplicada’, I + D + i 2008, ‘Subprograma de actuaciones Científicas y Tecnológicas en Parques Científicos y Tecnológicos’ (ACTEPARQ 2009) and FEDER. The CIBER de Enfermedades Raras is an initiative of the ISCIII. CDTI FEDER-Innterconecta EXP00052887/ITC-20111037.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof Molecular Autism. 2015 Apr 15;6:21
dc.rights © 2015 Codina-Solà et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Autisme -- Aspectes genètics
dc.title Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s13229-015-0017-0
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account


In collaboration with Compliant to Partaking