Alonso González, AitanaCalaza Cabanas, ManuelAmigo Lechuga, JorgeGonzález Peñas, JavierMartínez Regueiro, RocíoFernández Prieto, MontserratParellada, MaraArango, CelsoRodríguez Fontenla, María CristinaCarracedo Álvarez, Ángel2021-02-052021-02-052021Alonso-Gonzalez, A., Calaza, M., Amigo, J. et al. Exploring the biological role of postzygotic and germinal de novo mutations in ASD. Sci Rep 11, 319 (2021). https://doi.org/10.1038/s41598-020-79412-whttp://hdl.handle.net/10347/24388De novo mutations (DNMs), including germinal and postzygotic mutations (PZMs), are a strong source of causality for Autism Spectrum Disorder (ASD). However, the biological processes involved behind them remain unexplored. Our aim was to detect DNMs (germinal and PZMs) in a Spanish ASD cohort (360 trios) and to explore their role across different biological hierarchies (gene, biological pathway, cell and brain areas) using bioinformatic approaches. For the majority of the analysis, a combined ASD cohort (N = 2171 trios) was created using previously published data by the Autism Sequencing Consortium (ASC). New plausible candidate genes for ASD such as FMR1 and NFIA were found. In addition, genes harboring PZMs were significantly enriched for miR-137 targets in comparison with germinal DNMs that were enriched in GO terms related to synaptic transmission. The expression pattern of genes with PZMs was restricted to early mid-fetal cortex. In contrast, the analysis of genes with germinal DNMs revealed a spatio-temporal window from early to mid-fetal development stages, with expression in the amygdala, cerebellum, cortex and striatum. These results provide evidence of the pathogenic role of PZMs and suggest the existence of distinct mechanisms between PZMs and germinal DNMs that are influencing ASD riskeng© The Author(s) 2021. Open Access. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/GeneticsNeurosciencejournal article10.1038/s41598-020-79412-w2045-2322open access