Effects of Genetic Mutations Become Knowable with “Super Minigene” System

Molecular biologists at Iowa State University report the potential for the effects of genetic mutations to be known using a “super minigene” system developed in the lab of Ravindra Singh, PhD, Professor of Biomedical Sciences. The approach essentially enables scientists to reconstruct pathogenic mutations in a test tube and then see the effect of those mutations in different cells—meaning, no genetically engineered mouse models requiring sophisticated equipment and highly skilled technical staff. In a proof-of-concept study published January 12, 2024 in Nucleic Acids Research (DOI: 10.1093/nar/gkad1259), Singh’s group created a truncated version of the entire survival motor neuron 2 (SMN2) gene, associated with spinal muscular atrophy (SMA), a major genetic disease linked to infant mortality. The researchers  validated the utility of the super minigene in monitoring SMN protein levels upon splicing correction and showed how it could be employed to capture cell type-specific effects of a pathogenic SMN1 mutation. The open-access NAR article is titled “A Super Minigene with a Short Promoter and Truncated Introns Recapitulates Essential Features of Transcription and Splicing Regulation of the SMN1 and SMN2 Genes.”

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