Cellular Models and High-Throughput Screening for Genetic Causality of Intellectual Disability

Intellectual disabilities (ID) are a type of neurodevelopmental disorder (NDD). They can have a genetic cause, including an emerging class of ID centring around Rho GTPases, such as Ras-related C3 botulinum toxin substrate 1 (RAC1). Guidelines for establishing genetic causality include the use of cellular models, which often have morphological aberrations, a long-standing hallmark of ID. Disease cellular models can facilitate high-throughput screening (HTS) of chemical or genetic perturbations, which can provide translatable biological insight. Here, we discuss a class of IDs centring around RAC1. We review novel and established cellular models of ID, including mouse and human primary cells and reprogrammed or induced neurons. Finally, we review progress and remaining challenges in the adoption of HTS methodologies by the community studying neurological disorders.

Automated summary

Intellectual disabilities are a type of neurodevelopmental disorder that may have a genetic cause. The use of cellular models for establishing genetic causality and high-throughput screening of chemical or genetic perturbations can provide valuable insights. Researchers are exploring a class of intellectual disabilities centered around RAC1 and working on improving HTS methodologies for studying neurological disorders.