frameshift mutations

Up to 30% of mutations that cause human diseases are believed to generate in-frame nonsense codons. How the cell handles such deleterious transcripts can determine the severity of disease.

Cells are known to neutralize these transcripts in two ways: by triggering nonsense-mediated decay (NMD), a translation-dependent process that degrades transcripts containing premature truncation codons (PTCs), or nonsense-associated alternative splicing (NAS), in which offending exons are removed before splicing by a putative nuclear reading-frame scanning mechanism (see figure).

References

 Raes J, Van de Peer Y. Functional divergence of proteins through frameshift mutations. Trends Genet. 2005 Aug;21(8):428-31. PMID: 15951050