RT Journal Article
T1 Exploring the biological role of postzygotic and germinal de novo mutations in ASD
A1 Alonso González, Aitana
A1 Calaza Cabanas, Manuel
A1 Amigo Lechuga, Jorge
A1 González Peñas, Javier
A1 Martínez Regueiro, Rocío
A1 Fernández Prieto, Montserrat
A1 Parellada, Mara
A1 Arango, Celso
A1 Rodríguez Fontenla, María Cristina
A1 Carracedo Álvarez, Ángel
K1 Genetics
K1 Neuroscience
AB De 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 risk
PB Springer Nature
YR 2021
FD 2021
LK http://hdl.handle.net/10347/24388
UL http://hdl.handle.net/10347/24388
LA eng
NO Alonso-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-w
NO AA-G was supported by Fundación María José Jove. CR-F was supported by a contract from the FEDER. Instituto de Salud Carlos III/PI1900809/Cofinanciado FEDER supported this study
DS Minerva
RD 27 abr 2026