Genomic Strategies for Understanding the Pathophysiology of Autism Spectrum Disorder

Abstract

Recent breakthroughs in sequencing technology and technological developments have made it easier to analyze the entire human genome than ever before. In addition to disease-specific genetic mutations and chromosomal aberrations, epigenetic alterations in individuals can also be analyzed using genomics. Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) caused by genetic and/or environmental factors. More than a thousand genes associated with ASD have been identified which are known to be involved in brain development. However, it is difficult to decode the roles of ASD-associated genes without in vitro and in vivo validations, particularly in the process of brain development. In this review, we discuss genomic strategies for understanding the pathological mechanisms underlying ASD. For this purpose, we discuss ASD-associated genes and their functions, as well as analytical strategies and their strengths and weaknesses in cellular and animal models from a basic research perspective.

Keywords: animal model; autism spectrum disorder (ASD); behavior; cellular model; gene; genomics; morphology; mutation.

Figure 1

Summarized functions of ASD genes. Functional and related pathway information based on gene ontology of the latest SFARI ASD genes (1,031 genes released on January 11, 2022). SFARI Gene: https://www.sfari.org/resource/sfari-gene.

Figure 2

Genomic approaches to understand the mechanisms underlying ASD pathophysiology. To identify the genes involved in the pathophysiology of ASD, genome or gene expression analyses with samples such as blood and postmortem brains from individuals with ASD are performed to identify disease-specific mutations, chromosomal aberrations, and fragile genes. Cellular and animal models are used to analyze the genes identified in ASD individuals, and functional analyses are conducted based on the strength of each model.