Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function

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Casanova, M., Switala, A., Dandamudi, S., Hickman, A. R., Vandenbrink, J., Sharp, J. L., Feltus, F. A., & Casanova, M. F. (2019). Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function. Autism Research, 12(6), 860-869. https://doi.org/10.1002/aur.2112

Publication date: 26 Apr 2019 Added to AutiHub: 14 Sep 2026 Type: Article Article language: English
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Authors

Publication authors
8
Publication authors identified as autistic
1 / 8 (12.5%)
  1. Manuel Casanova *
  2. Andrew Switala
  3. Srini Dandamudi
  4. Allison R. Hickman
  1. Joshua Vandenbrink
  2. Julia L. Sharp
  3. Frank Alex Feltus
  4. Manuel F. Casanova

Abstract

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.

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Cited references
47
With a DOI
45
Without a DOI, from raw bibliography text
2
3 / 47 (6.4%) cited references include at least one author identified as autistic.
References with data to complete
0 / 47 (0.0%)
References with detected author names
47 / 47 (100.0%)
Without detected author names
0
Without a structured title
0
Without a stable identifier
2
References with raw author names still to review
0
References with external metadata lookup issues
0
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Author names detected in the cited bibliography
527
From DOI or external metadata
527
From validated raw bibliography text
0
Raw names already validated
0
Raw names still to review
0
15 / 527 (2.8%) names are linked to an author already present in AutiHub. 512 / 527 (97.2%) names are not yet linked.
Names linked to a person identified as autistic
3 / 527 (0.6%)
Calculated across all author names detected in the cited bibliography. Among names linked to an author already present in AutiHub: 3 / 15 (20.0%). Distinct people identified as autistic: 2 / 380 (0.5%).
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