Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder
| Title: | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder |
|---|---|
| Authors: | Lim ET; Uddin M; De Rubeis S; Chan Y; Kamumbu AS; Zhang X; D'Gama AM; Kim SN; Hill RS; Goldberg AP; Poultney C; Minshew NJ; Kushima I; Aleksic B; Ozaki N; Parellada M; Arango C; Penzol MJ; Carracedo A; Kolevzon A; Hultman CM; Weiss LA; Fromer M; Chiocchetti AG; Freitag CM; Church GM; Scherer SW; Buxbaum JD; Walsh CA; Autism Sequencing Consortium including Aleksic B; Anney R; Barbosa M; Barrett J; Betancur C; Bishop S; Brusco A; Chung BHY; Cook E; Coon H; Cutler DJ; Daly M; Doan R; Fernández-Prieto M; Ferrero GB; Gargus J; Geschwind D; Gill M; Gómez-Guerrero L; Hansen-Kiss E; He X; Herman G; Hertz-Picciotto I; Hultman C; Iliadou B; Ionita-Laza I; Jugessur A; Knudsen GP; Kosmicki J; Lee SL; Lehner T; Lennertz S; Lim E; Maciel P; Magnus P; Manoach D; Minshew N; Morrow E; Mulle J; Neale B; Palotie A; Passos-Bueno MR; Pericak-Vance M; Persico A; Pessah I; Reichenberg A; Reichert J; Renieri A; Robinson E; Samocha K; Sanders S; Sandin S; Santangelo SL; Satterstrom K; Schafer C; Schellenberg G; Scherer S; Senthil G; Silva M; Singh T; Siper PM; Soares G; Stevens C; Stoltenberg C; Surén P; Sutcliffe JS; Szatmari P; Tassone F; Thurm A; Walsh C; Weiss L; Werling D; Willsey J; Xu X; Yu TW; Yuen R; Zwick ME |
| Contributors: | Lim ET; Uddin M; De Rubeis S; Chan Y; Kamumbu AS; Zhang X; D'Gama AM; Kim SN; Hill RS; Goldberg AP; Poultney C; Minshew NJ; Kushima I; Aleksic B; Ozaki N; Parellada M; Arango C; Penzol MJ; Carracedo A; Kolevzon A; Hultman CM; Weiss LA; Fromer M; Chiocchetti AG; Freitag CM; Church GM; Scherer SW; Buxbaum JD; Walsh CA; Autism Sequencing Consortium including Aleksic B; Anney R; Barbosa M; Barrett J; Betancur C; Bishop S; Brusco A; Chung BHY; Cook E; Coon H; Cutler DJ; Daly M; Doan R; Fernández-Prieto M; Ferrero GB; Gargus J; Geschwind D; Gill M; Gómez-Guerrero L; Hansen-Kiss E; He X; Herman G; Hertz-Picciotto I; Hultman C; Iliadou B; Ionita-Laza I; Jugessur A; Knudsen GP; Kosmicki J; Lee SL; Lehner T; Lennertz S; Lim E; Maciel P; Magnus P; Manoach D; Minshew N; Morrow E; Mulle J; Neale B; Palotie A; Passos-Bueno MR; Pericak-Vance M; Persico A; Pessah I; Reichenberg A; Reichert J; Renieri A; Robinson E; Samocha K; Sanders S; Sandin S; Santangelo SL; Satterstrom K; Schafer C; Schellenberg G; Scherer S; Senthil G; Silva M; Singh T; Siper PM |
| Publication Year: | 2017 |
| Collection: | Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| Subject Terms: | Autism Spectrum Disorder; Databases; Genetic; Genetic Predisposition to Disease; Genetic Variation; Human; Mosaicism; Mutation; Missense; Zygote; Neuroscience (all) |
| Description: | We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/28714951; info:eu-repo/semantics/altIdentifier/wos/WOS:000408587700008; volume:20; issue:9; firstpage:1217; lastpage:1224; numberofpages:8; journal:NATURE NEUROSCIENCE; http://hdl.handle.net/2318/1659858; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85028454831; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672813/ |
| DOI: | 10.1038/nn.4598 |
| Availability: | http://hdl.handle.net/2318/1659858; https://doi.org/10.1038/nn.4598; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5672813/ |
| Rights: | info:eu-repo/semantics/openAccess |
| Accession Number: | edsbas.96A872BA |
| Database: | BASE |