In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a nonsense codon, or a premature stop codon in the transcribed mRNA, and leads to a truncated, incomplete, and possibly nonfunctional protein product.[1] Nonsense mutations are not always harmful;[2] the functional effect of a nonsense mutation depends on many aspects, such as the location of the stop codon within the coding DNA.[2] For example, the effect of a nonsense mutation depends on the proximity of the nonsense mutation to the original stop codon, and the degree to which functional subdomains of the protein are affected.[3] As nonsense mutations leads to premature termination of polypeptide chains; they are also called chain termination mutations.[4]
Missense mutations differ from nonsense mutations since they are point mutations that exhibit a single nucleotide change to cause substitution of a different amino acid. A nonsense mutation also differs from a nonstop mutation, which is a point mutation that removes a stop codon. About 10% of patients facing genetic diseases have involvement with nonsense mutations.[5] Some of the diseases that these mutations can cause are Duchenne muscular dystrophy (DMD), cystic fibrosis (CF),[6] spinal muscular atrophy (SMA), cancers, metabolic diseases, and neurologic disorders.[5][7] The rate of nonsense mutations is variable from gene-to-gene and tissue-to-tissue, but gene silencing occurs in every patient with a nonsense mutation.[5]
^Sharma, Jyoti; Keeling, Kim M.; Rowe, Steven M. (2020-08-15). "Pharmacological approaches for targeting cystic fibrosis nonsense mutations". European Journal of Medicinal Chemistry. 200: 112436. doi:10.1016/j.ejmech.2020.112436. ISSN 0223-5234. PMC 7384597. PMID 32512483.
^Balasubramanian, Suganthi; Fu, Yao; Pawashe, Mayur; McGillivray, Patrick; Jin, Mike; Liu, Jeremy; Karczewski, Konrad J.; MacArthur, Daniel G.; Gerstein, Mark (2017-08-29). "Using ALoFT to determine the impact of putative loss-of-function variants in protein-coding genes". Nature Communications. 8 (1): 382. Bibcode:2017NatCo...8..382B. doi:10.1038/s41467-017-00443-5. ISSN 2041-1723. PMC 5575292. PMID 28851873.
^Clark, David P.; Pazdernik, Nanette J.; McGehee, Michelle R. (2019), "Mutations and Repair", Molecular Biology, Elsevier, pp. 832–879, doi:10.1016/b978-0-12-813288-3.00026-4, ISBN 9780128132883, S2CID 239340633, retrieved 2022-12-02
^ abc"Nonsense mutation correction in human diseases an approach for targeted medicine | WorldCat.org". www.worldcat.org. Retrieved 2022-12-02.
^Guimbellot, Jennifer; Sharma, Jyoti; Rowe, Steven M. (November 2017). "Toward inclusive therapy with CFTR modulators: Progress and challenges". Pediatric Pulmonology. 52 (Suppl 48): S4–S14. doi:10.1002/ppul.23773. ISSN 8755-6863. PMC 6208153. PMID 28881097.
^Benhabiles, Hana; Jia, Jieshuang; Lejeune, Fabrice (2016-01-01), Benhabiles, Hana; Jia, Jieshuang; Lejeune, Fabrice (eds.), "Chapter 2 - Pathologies Susceptible to be Targeted for Nonsense Mutation Therapies", Nonsense Mutation Correction in Human Diseases, Boston: Academic Press, pp. 77–105, ISBN 978-0-12-804468-1, retrieved 2022-12-02
In genetics, a nonsensemutation is a point mutation in a sequence of DNA that results in a nonsense codon, or a premature stop codon in the transcribed...
mutations are a class of mutations which are changes to a single base. Missense and Nonsensemutations are two subtypes of point mutations. The rate of these...
to as nonsense codons. A nonstop mutation, also called a stop-loss variant, is a point mutation that occurs within a stop codon. Nonstop mutations cause...
latter case the mutation will have little or no effect on phenotype and therefore be neutral. A nonsensemutation is a point mutation in a sequence of...
in mutation rates for transitions (Alpha) and transversions (Beta). Transition mutations are about ten times more common than transversions. Nonsense mutations...
the most common norovirus strain, GII.4. Homozygous carriers of any nonsensemutation in the FUT2 gene are called non-secretors, as no ABH-antigen is produced...
contains a mutation that changes a codon for an amino acid in a protein to the nonsense stop codon TAG (see stop codon and nonsensemutation). If, upon...
inactive protein. This form of mutation is termed an early stop codon or a nonsensemutation. This is a genetic mutation at the level of nucleotide bases...
A nonsense suppressor is a factor which can inhibit the effect of the nonsensemutation. Nonsense suppressors can be generally divided into two classes:...
DNA sequence. Two other types of nonsynonymous substitution are the nonsensemutations, in which a codon is changed to a premature stop codon that results...
"proofreading" ability of DNA polymerases. Missense mutations and nonsensemutations are examples of point mutations that can cause genetic diseases such as sickle-cell...
male Samoyeds. Also known as hereditary nephritis, it is caused by a nonsensemutation in codon 1027 of the COL4A5 gene on the X chromosome (glycine to stop...
in the swap correlate. The premature insertion of a stop codon, a nonsensemutation, can alter the primary structure of a protein. In this case, a truncated...
Honeyman K, Agrawal S, et al. (July 1999). "Specific removal of the nonsensemutation from the mdx dystrophin mRNA using antisense oligonucleotides". Neuromuscular...
Union to treat people with Duchenne muscular dystrophy who have a nonsensemutation in the dystrophin gene, can walk, and are more than five years old...
needed] A nonsensemutation in one gene of an operon prevents the translation of subsequent genes in the unit. This effect is called mutational polarity...
and have only minor effects on disease risk. Severe variants (from nonsensemutations) are rare. The common MTHFR deficiencies are usually asymptomatic...
segment and the nodes of Ranvier during development. Patients with nonsensemutations in NFASC have abnormalities in the paranodal axo-glial junction (PNJ)...
depending on the kind of cell. Known mutations to the gene which can cause Donohue syndrome include a nonsensemutation that resulted in early termination...
transcript contains a premature termination codon (PTC) due to a nonsensemutation. If this codon occurs prior to the EJC site, the EJC will remain bound...
associated with mitochondrial myopathy. A G5920A mutation, and a heteroplasmic G6708A nonsensemutation have been associated with COX deficiency and RM-MT...
Liebhaber SA, Romão L (July 2004). "Nonsensemutations in close proximity to the initiation codon fail to trigger full nonsense-mediated mRNA decay". The Journal...
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