Editing Nonsense mutation (section)

{{Short description|Type of mutation in a DNA sequence}}
In [[genetics]], a '''nonsense mutation''' is a [[point mutation]] in a [[DNA sequence|sequence]] of [[DNA]] that results in a ''nonsense codon'', or a premature [[stop codon]] in the [[Transcription (genetics)|transcribed]] [[mRNA]], and leads to a truncated, incomplete, and possibly nonfunctional [[protein]] product.<ref name=":1">{{Cite journal |last1=Sharma |first1=Jyoti |last2=Keeling |first2=Kim M. |last3=Rowe |first3=Steven M. |title=Pharmacological approaches for targeting cystic fibrosis nonsense mutations |date=2020-08-15 |journal=European Journal of Medicinal Chemistry |volume=200 |pages=112436 |doi=10.1016/j.ejmech.2020.112436 |pmc=7384597 |pmid=32512483}}</ref> Nonsense mutations are not always harmful;<ref name=":11">{{Cite journal |last=Potapova |first=Nadezhda A. |date=2022-05-01 |title=Nonsense Mutations in Eukaryotes |url=https://doi.org/10.1134/S0006297922050029 |journal=Biochemistry (Moscow) |language=en |volume=87 |issue=5 |pages=400–412 |doi=10.1134/S0006297922050029 |pmid=35790376 |s2cid=248793651 |issn=1608-3040|url-access=subscription }}</ref> the functional effect of a nonsense mutation depends on many aspects, such as the location of the [[stop codon]] within the coding [[DNA]].<ref name=":11" /> 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.<ref>{{Cite journal |last1=Balasubramanian |first1=Suganthi |last2=Fu |first2=Yao |last3=Pawashe |first3=Mayur |last4=McGillivray |first4=Patrick |last5=Jin |first5=Mike |last6=Liu |first6=Jeremy |last7=Karczewski |first7=Konrad J. |last8=MacArthur |first8=Daniel G. |last9=Gerstein |first9=Mark |date=2017-08-29 |title=Using ALoFT to determine the impact of putative loss-of-function variants in protein-coding genes |journal=Nature Communications |volume=8 |issue=1 |pages=382 |doi=10.1038/s41467-017-00443-5 |pmc=5575292 |pmid=28851873|bibcode=2017NatCo...8..382B }}</ref> As nonsense mutations leads to premature termination of [[polypeptide chain]]s; they are also called chain termination mutations.<ref name=":2">{{Citation |last1=Clark |first1=David P. |title=Mutations and Repair |date=2019 |url=http://dx.doi.org/10.1016/b978-0-12-813288-3.00026-4 |work=Molecular Biology |pages=832–879 |publisher=Elsevier |access-date=2022-12-02 |last2=Pazdernik |first2=Nanette J. |last3=McGehee |first3=Michelle R.|doi=10.1016/b978-0-12-813288-3.00026-4 |isbn=9780128132883 |s2cid=239340633 |url-access=subscription }}</ref>

[[Missense mutation]]s differ from nonsense mutations since they are [[point mutation]]s that exhibit a single [[nucleotide]] change to cause substitution of a different [[amino acid]]. A nonsense mutation also differs from a [[Stop codon#Nonstop|nonstop mutation]], which is a point mutation that removes a stop codon. About 10% of patients facing genetic diseases have involvement with nonsense mutations.<ref name=":3">{{Cite web |title=Nonsense mutation correction in human diseases an approach for targeted medicine {{!}} WorldCat.org |url=https://www.worldcat.org/title/1281858870 |access-date=2022-12-02 |website=www.worldcat.org |language=en}}</ref> Some of the diseases that these mutations can cause are [[Duchenne muscular dystrophy]] (DMD), [[cystic fibrosis]] (CF),<ref>{{Cite journal |last1=Guimbellot |first1=Jennifer |last2=Sharma |first2=Jyoti |last3=Rowe |first3=Steven M. |date=November 2017 |title=Toward inclusive therapy with CFTR modulators: Progress and challenges |journal=Pediatric Pulmonology |volume=52 |issue=Suppl 48 |pages=S4–S14 |doi=10.1002/ppul.23773 |pmc=6208153 |pmid=28881097}}</ref> [[spinal muscular atrophy]] (SMA), [[cancer]]s, [[metabolic diseases]], and [[Neurological disorder|neurologic disorders.]]<ref name=":3" /><ref>{{Citation |last1=Benhabiles |first1=Hana |title=Ch. 2. Pathologies Susceptible to be Targeted for Nonsense Mutation Therapies |date=2016-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780128044681000026 |work=Nonsense Mutation Correction in Human Diseases |pages=77–105 |editor-last=Benhabiles |editor-first=Hana |place=Boston |publisher=Academic Press |language=en |isbn=978-0-12-804468-1 |access-date=2022-12-02 |last2=Jia |first2=Jieshuang |last3=Lejeune |first3=Fabrice |editor2-last=Jia |editor2-first=Jieshuang |editor3-last=Lejeune |editor3-first=Fabrice}}</ref> 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.<ref name=":3" />