The Use of Next-Generation Sequencing for Research and Diagnostics for Intellectual Disability

Abstract

Genetic or genomic mutation is a major cause of intellectual disability (ID). However, despite the generally anticipated strong genotype/phenotype correlation for ID, there are huge obstacles to gene identification, except perhaps where very distinct syndromic features are observed, because of the high degree of genetic heterogeneity and wide variability of phenotype for different mutations or even with the same mutation within a single gene. A recent review estimates in excess of 2500 genes for ID. Fortunately for researchers and diagnosticians alike, the recent advent of massively parallel sequencing technologies, or next-generation sequencing (NGS) has made an apparently impossible task tractable. Here, we review the ongoing research endeavors to identify new disease genes, as well as strategies and approaches at the clinical level.

Figure 1.

Number of publications in PubMed using the search terms “next-generation sequencing,” “autism spectrum disorder” (ASD), “intellectual disability” (ID), “epileptic encephalopathy” (EE), “schizophrenia” (SCZ), and “bipolar disorder” (BD) annually since 2009. For 2016, as PubMed was accessed on August 6, 2016 and thus represents an incomplete year, a factor of 2 was multiplied as an adjustment factor.

Figure 2.

Number of hits or publications per year in Google Scholar broken down into sequencing strategy, using the search terms “intellectual disability” + “whole-exome sequencing” (labeled WES), “intellectual disability” + “whole-genome sequencing” (labeled WGS), “intellectual disability” + “targeted sequencing” (labeled “Targeted sequencing”), “intellectual disability” + “somatic mutations” (labeled “Somatic mutations”), and “intellectual disability” + “X-linked” + “sequencing” (labeled “X-linked”).