Next-Generation Sequencing in Autism Spectrum Disorder

Cold Spring Harb Perspect Med. 2019 Aug 1;9(8):a026872. doi: 10.1101/cshperspect.a026872.


Autism spectrum disorder (ASD) is a common disorder that causes substantial distress. Heritability studies consistently show a strong genetic contribution, raising the hope that identifying ASD-associated genetic variants will offer insights into neurobiology and ultimately therapeutics. Next-generation sequencing (NGS) enabled the identification of disruptive variants throughout protein-coding regions of the genome. Alongside large cohorts and novel statistical methods, these NGS methods revolutionized ASD gene discovery. NGS methods have also contributed substantially to functional genetic data, such as gene expression, used to understand the neurobiological consequences of disrupting these ASD-associated genes. These functional data are also critical for annotating the noncoding genome as whole-genome sequencing (WGS) begins to provide initial insights outside of protein-coding regions. NGS methods still have a major role to play, as do similarly transformative advances in stem cell and gene-editing methods, in translating genetic discoveries into a first generation of ASD therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics*
  • Disease Models, Animal
  • Genetic Predisposition to Disease*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Mutation, Missense
  • Whole Genome Sequencing