• Ten things you didn't know about Wikipedia •

Nonsense mutation

From Wikipedia, the free encyclopedia

It has been suggested that this article or section be merged into mutation. (Discuss)

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.

[hide]

[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 and protein product would be:

   mRNA: AUG ACU CAC UGA CGC CGU AGC UGA
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

Nonsense mutations can cause a genetic disease by damaging a gene responsible for a specific protein, for example, distrophin in Duchenne muscular dystrophy. The same disease may, however, be caused by other kinds of damage to the same gene. Examples of diseases in which nonsense mutations are known to be among the causes include:

Cystic fibrosis (caused by mutations in the cystic fibrosis transmembrane conductance regulator gene).

Duchenne muscular dystrophy (distrophin)

Beta thalassaemia

Hurler syndrome

An experimental drug known as PTC124 may be useful in treating some cases of each of the above diseases (that is, the cases caused by a nonsense mutation). PTC124 is scheduled to enter the final phase of clinical trials in 2007.[1]

[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
Welch EM, et al., "PTC124 targets genetic disorders caused by nonsense mutations", Nature 447, 87-91 (3 May 2007) (DOI: 10.1038/nature05756)

Retrieved from "http://en.wikipedia.org/wiki/Nonsense_mutation"

Categories: Articles to be merged since February 2007 | Mutation

Views

Personal tools

interaction

Search

Toolbox

In other languages

Your continued donations keep Wikipedia running!

• Ten things you didn't know about Wikipedia •

Missense mutation

From Wikipedia, the free encyclopedia

Jump to: navigation, search

It has been suggested that this article or section be merged into mutation. (Discuss)

In genetics, missense mutations or nonsynonymous mutations are types of point mutations where a single nucleotide is changed to cause substitution of a different amino acid. This in turn can render the resulting protein nonfunctional. Such mutations are responsible for diseases such as Epidermolysis bullosa, sickle-cell disease, and SOD1 mediated ALS(Boillée 2006, p. 39).

For example, in sickle-cell disease, the 17th nucleotide of the gene for the beta chain of hemoglobin found on chromosome 11 is erroneously changed from the codon GAG (for glutamic acid) to GTG (which codes valine), so the 6th amino acid is incorrectly substituted.

Not all missense mutations lead to appreciable protein changes. An amino acid may be replaced by an amino acid of very similar chemical properties, in which case, the protein may still function normally; this is termed a neutral or "quiet" mutation. When an amino acid may be encoded by more than one codon (so-called "degenerate coding") a mutation in a codon may not produce any change in translation; this would be a synonymous mutation and not a missense mutation.

[edit] References

Boillée, Séverine (2006), "ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors", Neuron 52 (1): 39-59.

Missense mutation

Tuesday, August 28, 2007