Researchers identify hundreds of genes vital to early brain development, but find that only a small number linked to known disorders, suggesting many genetic causes of autism and developmental delay have yet to be discovered

Researchers at the Hebrew University of Jerusalem have identified hundreds of genes essential to early brain development and uncovered a previously unknown genetic disorder linked to severe neurodevelopmental impairment, according to a study published in Nature Neuroscience.

The study used large-scale CRISPR gene-editing screens to systematically shut down nearly all genes in mouse embryonic stem cells as they developed into neurons. The approach allowed scientists to pinpoint which genes are critical for the formation, differentiation and migration of nerve cells — processes that, when disrupted, can lead to autism and other neurodevelopmental disorders.

Led by Prof. Sagiv Shifman, the research team found that hundreds of genes are indispensable for normal neuronal development, yet only a small fraction are currently associated with known neurodevelopmental disorders. The findings suggest that many disease-causing genes remain undiscovered.

The researchers also identified clear patterns in how different genes contribute to disease. Genes that regulate other genes, such as transcription and chromatin regulators, were more often linked to dominant disorders, where a mutation in a single copy of a gene can cause illness. In contrast, genes involved in metabolic processes were typically associated with recessive disorders, requiring mutations in both copies of the gene.