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Information about Nonsense Mutation

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.

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.

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.

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: 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]

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)
Genetics is the science of heredity and variation in living organisms.[1][2] Knowledge of the inheritance of characteristics has been implicitly used since prehistoric times for improving crop plants and animals through selective breeding.
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A point mutation, or single base substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide. One can categorize point mutations as follows:
  • transitions

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DNA sequence or genetic sequence is a succession of letters representing the primary structure of a real or hypothetical DNA molecule or strand, with the capacity to carry information.
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In the genetic code, a stop codon (or termination codon) is a nucleotide triplet within messenger RNA that signals a termination of translation.[1] Proteins are unique sequences of amino acids, and most codons in messenger RNA correspond to the addition of an
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Transcription is the process through which a DNA sequence is enzymatically copied by an RNA polymerase to produce a complementary RNA. So to say, it is the transfer of genetic information from DNA into RNA.
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Messenger Ribonucleic Acid (mRNA) is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes.
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In mathematics, truncation is the term for limiting the number of digits right of the decimal point, by discarding the least significant ones.

For example, consider the real numbers

5.6341432543653654
32.438191288
6.

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Proteins are large organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues.
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Sense, when applied in a molecular biology context, is a general concept used to compare the polarity of nucleic acid molecules, particularly RNA, to other nucleic acid molecules. Depending on the context within molecular biology, sense may have slightly different meanings.
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Methionine (abbreviated as Met or M)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. This essential amino acid is classified as nonpolar.
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Threonine (abbreviated as Thr or T)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)CH(OH)CH3. Its codons are ACU and ACA. This essential amino acid is classified as polar.
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Histidine (abbreviated as His or H)[1] is one of the 20 most common natural amino acids present in proteins. In the nutritional sense, in humans, histidine is considered an essential amino acid, but mostly only in children.
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Arginine (abbreviated as Arg or R)[1] is an α-amino acid. The L -form is one of the 20 most common natural amino acids. Its codons are CGU, CGC, CGA and CGG.
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Alanine (abbreviated as Ala or A)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)CH3. The L-isomer is one of the 20 proteinogenic amino acids, i.e. the building blocks of proteins.
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Arginine (abbreviated as Arg or R)[1] is an α-amino acid. The L -form is one of the 20 most common natural amino acids. Its codons are CGU, CGC, CGA and CGG.
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Serine (abbreviated as Ser or S)[1] is an organic compound with the formula HO2CCH(NH2)CH2OH. It is one of the 20 naturally occurring proteinogenic amino acids. Its codons are UCU, UCC, UCA, UCG, AGU and AGC.
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Not to be confused with cysteine.


Cytosine is one of the five main nucleobases found in the nucleic acids DNA and RNA. It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an amine group at position 4 and
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5-methyluracil a pyrimidine nucleobase. As the name implies, thymine may be derived by methylation of uracil at the 5th carbon. In RNA thymine is replaced with uracil in most cases.
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Methionine (abbreviated as Met or M)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. This essential amino acid is classified as nonpolar.
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Threonine (abbreviated as Thr or T)[1] is an α-amino acid with the chemical formula HO2CCH(NH2)CH(OH)CH3. Its codons are ACU and ACA. This essential amino acid is classified as polar.
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Histidine (abbreviated as His or H)[1] is one of the 20 most common natural amino acids present in proteins. In the nutritional sense, in humans, histidine is considered an essential amino acid, but mostly only in children.
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Ascomycota (sac fungi)
  • Saccharomycotina (true yeasts)
  • Taphrinomycotina
  • Schizosaccharomycetes (fission yeasts)
Basidiomycota (club fungi)
  • Urediniomycetes

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Nonsense mediated decay (NMD) is a cellular mechanism of mRNA surveillance to detect nonsense mutations and prevent the expression of truncated or erroneous proteins. NMD is triggered by exon-junction complexes (EJC), that have been formed during pre-RNA processing, being
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MeSH D020388 Duchenne muscular dystrophy (DMD) (also known as muscular dystrophy - Duchenne type) is an eventually fatal disorder that is characterized by rapidly progressive muscle weakness and atrophy of muscle tissue.
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Cystic fibrosis
Classification & external resources

ICD-10 E 84.
ICD-9 277

OMIM 219700
DiseasesDB 3347
MedlinePlus 000107
eMedicine ped/535  
MeSH D003550 Cystic fibrosis (CF
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Cystic fibrosis transmembrane conductance regulator (CFTR) is an ABC transporter-class protein and ion channel that transports chloride ions across epithelial cell membranes.
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MeSH D020388 Duchenne muscular dystrophy (DMD) (also known as muscular dystrophy - Duchenne type) is an eventually fatal disorder that is characterized by rapidly progressive muscle weakness and atrophy of muscle tissue.
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Thalassemia
Classification & external resources

MedlinePlus 000587
eMedicine ped/2229   radio/686

Thalassemia (British spelling, "thalassaemia") is an inherited autosomal recessive blood disease.
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Hurler syndrome
Classification & external resources

ICD-10 E 76.0
ICD-9 277.5

eMedicine ped/1031   Hurler syndrome, also known as mucopolysaccharidosis type I (MPS I), Hurler's disease and gargoylism[1]
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