Advances in Autism Research – The Genomic Basis of ASD

Many of the recent advances in autism research that have provided fundamental insight into this condition have come from the application of genetic/genomic approaches; these advances have been fomented by the advent of new technologies to interrogate the en‐ tire genome, such as array comparative genomic hybridization (aCGH), single nucleotide polymorphism (SNP) microarrays, transcriptome sequencing, and whole genome or whole exome sequencing (WGS/WES) [1]. With the recent advancement of these technol‐ ogies over more traditional, lower-resolution technologies such as cytogenetic analysis, came the ability to interrogate the entire genome at a high-resolution. With the improve‐ ment of next-generation sequencing technology, as well as the reduction in the cost of this technique, WGS is becoming more commonplace in the search for novel diseasecausing variants in individual patients. Alternatively, many studies have utilized WES, as it is less costly than sequencing the entire genome and coding simple nucleotide var‐ iants (SNVs) can often be more readily interpreted given knowledge provided by the ge‐ netic code. While the reduced cost and more readily interpretable variation have proven to be distinct advantages of this method over whole-genome sequencing, it is well known that many other variants in non-coding or regulatory regions can be pathogenic, and they typically cannot be discerned by whole-exome sequencing, which requires a targeted-capture step to enrich for and focus analysis on the coding sequences of all an‐ notated protein-coding genes [2, 3]. Furthermore, repetitive or G-C rich regions or highly homologous sequences are often excluded by WES, and copy number variations (CNVs) usually cannot be accurately called due to the use of PCR-based sample preparation methods. Nonetheless, the utility of WGS/WES in individual patient diagnosis and man‐ agement has been demonstrated by several recent reports [4-6].