Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function.
DNA transposons
central nervous system
developmental
genes
retroelements
Journal
Autism research : official journal of the International Society for Autism Research
ISSN: 1939-3806
Titre abrégé: Autism Res
Pays: United States
ID NLM: 101461858
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
01
10
2018
revised:
22
03
2019
accepted:
06
04
2019
pubmed:
27
4
2019
medline:
28
7
2020
entrez:
27
4
2019
Statut:
ppublish
Résumé
Previous research on autism risk (ASD), developmental regulatory (DevReg), and central nervous system (CNS) genes suggests they tend to be large in size, enriched in nested repeats, and mutation intolerant. The relevance of these genomic features is intriguing yet poorly understood. In this study, we investigated the feature landscape of these gene groups to discover structural themes useful in interpreting their function, developmental patterns, and evolutionary history. ASD, DevReg, CNS, housekeeping, and whole genome control (WGC) groups were compiled using various resources. Multiple gene features of interest were extracted from NCBI/UCSC Bioinformatics. Residual variation intolerance scores, Exome Aggregation Consortium pLI scores, and copy number variation data from Decipher were used to estimate variation intolerance. Gene age and protein-protein interactions (PPI) were estimated using Ensembl and EBI Intact databases, respectively. Compared to WGC: ASD, DevReg, and CNS genes are longer, produce larger proteins, maintain greater numbers/density of conserved noncoding elements and transposable elements, produce more transcript variants, and are comparatively variation intolerant. After controlling for gene size, mutation tolerance, and clinical association, ASD genes still retain many of these same features. In addition, we also found that ASD genes that are extremely mutation intolerant have larger PPI networks. These data support many of the recent findings within the field of autism genetics but also expand our understanding of the evolution of these broad gene groups, their potential regulatory complexity, and the extent to which they interact with the cellular network. Autism Res 2019, 12: 860-869. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism risk genes are more ancient compared to other genes in the genome. As such, they exhibit physical features related to their age, including long gene and protein size and regulatory sequences that help to control gene expression. They share many of these same features with other genes that are expressed in the brain and/or are associated with prenatal development.
Identifiants
pubmed: 31025836
doi: 10.1002/aur.2112
pmc: PMC6613973
mid: NIHMS1024256
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
860-869Subventions
Organisme : NICHD NIH HHS
ID : R01 HD065279
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH086784
Pays : United States
Organisme : Autism Research Institute
Pays : International
Informations de copyright
© 2019 International Society for Autism Research, Wiley Periodicals, Inc.
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