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. 2023 Aug 26;24(17):13248.
doi: 10.3390/ijms241713248.

Structural Variations Contribute to the Genetic Etiology of Autism Spectrum Disorder and Language Impairments

Rohan Alibutud  1 , Sammy Hansali  1 , Xiaolong Cao  1 , Anbo Zhou  1 , Vaidhyanathan Mahaganapathy  1 , Marco Azaro  1 , Christine Gwin  1 , Sherri Wilson  1 , Steven Buyske  2 , Christopher W Bartlett  3   4 , Judy F Flax  1 , Linda M Brzustowicz  1   5 , Jinchuan Xing  1   5
Affiliations

Structural Variations Contribute to the Genetic Etiology of Autism Spectrum Disorder and Language Impairments

Rohan Alibutud et al. Int J Mol Sci. .

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restrictive interests and/or repetitive behaviors and deficits in social interaction and communication. ASD is a multifactorial disease with a complex polygenic genetic architecture. Its genetic contributing factors are not yet fully understood, especially large structural variations (SVs). In this study, we aimed to assess the contribution of SVs, including copy number variants (CNVs), insertions, deletions, duplications, and mobile element insertions, to ASD and related language impairments in the New Jersey Language and Autism Genetics Study (NJLAGS) cohort. Within the cohort, ~77% of the families contain SVs that followed expected segregation or de novo patterns and passed our filtering criteria. These SVs affected 344 brain-expressed genes and can potentially contribute to the genetic etiology of the disorders. Gene Ontology and protein-protein interaction network analysis suggested several clusters of genes in different functional categories, such as neuronal development and histone modification machinery. Genes and biological processes identified in this study contribute to the understanding of ASD and related neurodevelopment disorders.

Keywords: autism spectrum disorder; copy number variation; family cohort; language impairment; microarray genotyping; neurodevelopmental disorder; structural variation; whole-genome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Workflow for candidate CNVs and gene identification.
Figure 2
Figure 2
Candidate syndromic CNVs at the 1q21.1 locus. Genome Browser tracks show the 1q21.1 duplication syndrome locus (red), the duplication in the patient called by PennCNV (DUP_1, green) and the duplication called by QuantiSNP (DUP_2, blue).
Figure 3
Figure 3
Workflow for candidate SV/MEIs and genes identification.
Figure 4
Figure 4
PPI Network for candidate genes. PPI network of 116 candidate genes. PPI network edges were defined by three databases: ConsensusPathDB (C), STRING (S), and GIANT_v2 (G). Edges defined by multiple databases are denoted as M. Genes that are also present in the known NDD gene list are colored accordingly (see Methods Section 4.12 for details).
See this image and copyright information in PMC

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