ABSTRACT
We discuss in this chapter how nonsense-mediated mRNA decay (NMD) affects the expression of human genetic diseases resulting from premature termination codons (PTCs) by considering how NM D alters disease phenotype. NM D may exert a beneficial, neutral, or harmful effect, depending on the location of the PTC in the transcript and the properties of the truncated protein. In the case of many PTCs, the resulting truncated protein might be nonfunctional and could be degraded without harmful effects. In these in stances, NM D probably does not significandy influence phenotype. In other cases, NM D can prevent expression of potentially dominant negative proteins. Therefore, NM D can sometimes exert a protective effect that benefits heterozygous carriers of PTCs. NM D can also contribute to a disease phenotype when it inhibits expression of partially functional proteins. Therapies that could affect gene expression in such cases are under development and may, in the future, provide avenues for effective clinical treatment of diseases that involve NM D.
