Type of mutation in a DNA sequence
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 .
^ a b Potapova, Nadezhda A. (2022-05-01). "Nonsense Mutations in Eukaryotes" . Biochemistry (Moscow) . 87 (5): 400–412. doi :10.1134/S0006297922050029 . ISSN 1608-3040 . PMID 35790376 . S2CID 248793651 .
^ 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
^ a b c "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