A Massively Parallel Screen of 5'UTR Mutations Identifies Variants Impacting Translation and Protein Production in Neurodevelopmental Disorder Genes.

ABSTRACT: De novo mutations cause a variety of neurodevelopmental disorders including autism. Recent whole genome sequencing from individuals with autism has shown that many de novo mutations also occur in untranslated regions (UTRs) of genes, but it is difficult to predict from sequence alone which mutations are functional, let alone causal. Therefore, we developed a high throughput assay to screen the transcriptional and translational effects of 997 variants from 5'UTR patient mutations. This assay successfully enriched for elements that alter reporter translation, identifying over 100 potentially functional mutations from probands. Studies in patient-derived cell lines further confirmed that these mutations can alter protein production in individuals with autism, and some variants f

SUBMITTER: Plassmeyer SP 

PROVIDER: S-EPMC10635273 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature