Nonsense mutation

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In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and possibly a truncated, and often nonfunctional protein product.

Contents 1 Simple example 2 Nonsense-mediated mRNA decay 3 Pathology associated with nonsense mutations 4 External links and references

[edit] Simple example

For example, given the following sense DNA sequence, the corresponding mRNA transcript, and the translated protein product:

    DNA: ATG ACT CAC CGA GCG CGA AGC TGA
   mRNA: AUG ACU CAC CGA GCG CGA AGC UGA
Protein: Met Thr His Arg Ala Arg Ser Stop

Suppose that a nonsense mutation were introduced at the fourth triplet in the DNA sequence (CGA) causing the cytosine to be replaced with thymine, yielding TGA in the DNA sequence. Since TGA is transcribed as UGA, the resulting transcript would be:

   mRNA: AUG ACU CAC UGA CGC CGU AGC UGA

Furthermore, the resulting protein product would be prematurely stopped since UGA is a stop codon:

 Protein: Met Thr His Stop

The remaining codons of the mRNA are not translated into amino acids because the stop codon is prematurely reached during translation. This can yield a truncated abbreviated protein product, which quite often lacks the functionality of the normal, non-mutant protein.

[edit] Nonsense-mediated mRNA decay

Despite an expected tendency for premature termination codons to yield shortened polypeptide products, in fact the formation of truncated proteins does not occur often in vivo. Many organisms -- including humans and lower species, such as yeast -- employ a nonsense-mediated mRNA decay pathway, which degrades mRNAs containing nonsense mutations before they are translated into nonfunctional polypeptides.

[edit] Pathology associated with nonsense mutations

• Cystic fibrosis - though rare, a nonsense mutation in the cystic fibrosis transmembrane conductance regulator gene can cause the disease

[edit] External links and references

• Mutations
• Nonsense mutation (Medical dictionary)
• Gatfield D, Unterholzner L, Ciccarelli FD, Bork P, Izaurralde E. "Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways". EMBO J. 2003 Aug 1;22(15):3960-70. PMID 12881430