Editing Mutation (section)

=== By effect on structure ===
[[File:Chromosomes mutations-en.svg|thumb|right|301px|Five types of chromosomal mutations]]
[[File:Deletion Insertion Substitution-en.svg|thumb|right|301px|Types of small-scale mutations]]

The sequence of a gene can be altered in a number of ways.<ref>{{cite web| vauthors = Rahman N |title=The clinical impact of DNA sequence changes|url=http://www.thetgmi.org/genetics/clinical-impact-dna-sequence-changes/|website=Transforming Genetic Medicine Initiative|access-date=27 June 2017|url-status=dead|archive-url=https://web.archive.org/web/20170804060005/http://www.thetgmi.org/genetics/clinical-impact-dna-sequence-changes/|archive-date=4 August 2017}}</ref> Gene mutations have varying effects on health depending on where they occur and whether they alter the function of essential proteins.
Mutations in the structure of genes can be classified into several types.{{citation needed|date=February 2024}}

==== Large-scale mutations ====
{{See also|Chromosome abnormality}}

Large-scale mutations in [[chromosome|chromosomal]] structure include:
* Amplifications (or [[gene duplication]]s) or repetition of a chromosomal segment or presence of extra piece of a chromosome broken piece of a chromosome may become attached to a homologous or non-homologous chromosome so that some of the genes are present in more than two doses leading to multiple copies of all chromosomal regions, increasing the dosage of the genes located within them.
* [[Polyploidy]], duplication of entire sets of chromosomes, potentially resulting in a separate breeding population and [[speciation]].
* Deletions of large chromosomal regions, leading to loss of the genes within those regions.
* Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially bringing together separate genes to form functionally distinct [[fusion gene]]s (e.g., [[Philadelphia chromosome|bcr-abl]]).
* Large scale changes to the structure of [[chromosome]]s called [[chromosomal rearrangement]] that can lead to a decrease of fitness but also to speciation in isolated, inbred populations. These include:
** [[Chromosomal translocation]]s: interchange of genetic parts from nonhomologous chromosomes.
** [[Chromosomal inversion]]s: reversing the orientation of a chromosomal segment.
** Non-homologous [[chromosomal crossover]].
** Interstitial deletions: an intra-chromosomal deletion that removes a segment of DNA from a single chromosome, thereby apposing previously distant genes. For example, cells isolated from a human [[astrocytoma]], a type of brain tumour, were found to have a chromosomal deletion removing sequences between the Fused in [[Glioblastoma]] (FIG) gene and the receptor tyrosine kinase (ROS), producing a fusion protein (FIG-ROS). The abnormal FIG-ROS fusion protein has constitutively active kinase activity that causes [[Carcinogenesis|oncogenic]] transformation (a transformation from normal cells to cancer cells).
* [[Loss of heterozygosity]]: loss of one [[allele]], either by a deletion or a genetic recombination event, in an organism that previously had two different alleles.

==== Small-scale mutations ====

Small-scale mutations affect a gene in one or a few nucleotides. (If only a single nucleotide is affected, they are called [[point mutation]]s.) Small-scale mutations include:
* [[Insertion (genetics)|Insertions]] add one or more extra nucleotides into the DNA. They are usually caused by [[transposable element]]s, or errors during replication of repeating elements. Insertions in the coding region of a gene may alter [[RNA splicing|splicing]] of the [[Messenger RNA|mRNA]] ([[splice site mutation]]), or cause a shift in the [[reading frame]] ([[Frameshift mutation|frameshift]]), both of which can significantly alter the [[gene product]]. Insertions can be reversed by excision of the transposable element.
* [[Deletion (genetics)|Deletions]] remove one or more nucleotides from the DNA. Like insertions, these mutations can alter the reading frame of the gene. In general, they are irreversible: Though exactly the same sequence might, in theory, be restored by an insertion, transposable elements able to revert a very short deletion (say 1–2 bases) in ''any'' location either are highly unlikely to exist or do not exist at all.
* [[Point mutation|Substitution mutations]], often caused by chemicals or malfunction of DNA replication, exchange a single nucleotide for another.<ref>{{cite journal | vauthors = Freese E | title = The Difference Between Spontaneous and Base-Analogue Induced Mutations of Phage T4 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 45 | issue = 4 | pages = 622–33 | date = April 1959 | pmid = 16590424 | pmc = 222607 | doi = 10.1073/pnas.45.4.622 | author-link = Ernst Freese | bibcode = 1959PNAS...45..622F | doi-access = free }}</ref> These changes are classified as transitions or transversions.<ref>{{cite journal | vauthors = Freese E | date = June 1959 |title=The specific mutagenic effect of base analogues on Phage T4 |journal=Journal of Molecular Biology |volume=1 |issue=2 |pages=87–105 |doi=10.1016/S0022-2836(59)80038-3}}</ref> Most common is the transition that exchanges a purine for a purine (A ↔ G) or a [[pyrimidine]] for a pyrimidine, (C ↔ T). A transition can be caused by nitrous acid, base mispairing, or mutagenic base analogues such as BrdU. Less common is a transversion, which exchanges a purine for a pyrimidine or a pyrimidine for a purine (C/T ↔ A/G). An example of a transversion is the conversion of [[adenine]] (A) into a cytosine (C). Point mutations are modifications of single base pairs of DNA or other small base pairs within a gene. A point mutation can be reversed by another point mutation, in which the nucleotide is changed back to its original state (true reversion) or by second-site reversion (a complementary mutation elsewhere that results in regained gene functionality). As discussed [[#By impact on protein sequence|below]], point mutations that occur within the protein [[coding region]] of a gene may be classified as [[Synonymous substitution|synonymous]] or [[nonsynonymous substitution]]s, the latter of which in turn can be divided into [[Missense mutation|missense]] or [[nonsense mutations]].