Abstract
Intellectual disability is the most common developmental disorder characterized by a congenital limitation in intellectual functioning and adaptive behavior. It often co-occurs with other mental conditions like attention deficit/hyperactivity disorder and autism spectrum disorder, and can be part of a malformation syndrome that affects other organs. Considering the heterogeneity of its causes (environmental and genetic), its frequency worldwide varies greatly. This review focuses on known genes underlying (syndromic and non-syndromic) intellectual disability, it provides a succinct analysis of their Gene Ontology, and it suggests the use of transcriptional profiling for the prioritization of candidate genes.
Highlights
The advances in scientific technology related to gene sequencing and discovery in recent years, such as high-throughput whole genome sequencing (WGS) and single-cell sequencing, have led to an increasing number of studies aimed at finding new causative genes for human diseases
To date, more than 800 genes are known to be involved in the pathogenesis of syndromic and nonsyndromic conditions with intellectual disability (ID), and the functions of their respective proteins are very different
Since 800 out of ~4500 human disease genes currently listed in OMIM is ~18%, if we suppose that the same proportion of all human genes (~20,000) is related to ID, this would suggest that up to 3500 human genes could cause a Mendelian condition that includes ID as one of its components
Summary
The advances in scientific technology related to gene sequencing and discovery in recent years, such as high-throughput whole genome sequencing (WGS) and single-cell sequencing, have led to an increasing number of studies aimed at finding new causative genes for human diseases. This confers multiple levels of interpretation to the GO analysis, the increasing number of parent/child terms does not always add useful information[50,51] To overcome this issue, DAVID functional annotation results, together with their relative p values and fold enrichment values (see Supplementary Table 3f), were further used for REViGO (Reduce + Visualize Gene Ontology) analysis (http://revigo.irb.hr/)[52]. Depending on the available resources, including bioinformatic support, either a large panel of known or candidate ID genes can be screened (as shown by 48) or the (currently known) human exome (WES) or genome (WGS) could be investigated These latter approaches can potentially identify “new genes” responsible for ID, the number of variants identified in each patient is challenging and not always interpreted[41]. We ranked all 20,588 annotated genes by decreasing BR and found that approximately 8% of all protein-coding genes have a BR above 2 but that approximately 10% of the 818 ID genes and approximately 25% of all XLID genes have a BR above
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