Editing Mutation (section)

=== By impact on protein sequence ===
[[File:Gene structure eukaryote 2 annotated.svg|alt=Diagram of the structure of a eukaryotic protein-coding gene, showing regulatory regions, introns, and coding regions. Four stages are shown: DNA, initial mRNA product, mature mRNA, and protein.|thumb|460x460px|The structure of a [[eukaryotic]] protein-coding gene. A mutation in the [[protein coding region]] (red) can result in a change in the amino acid sequence. Mutations in other areas of the gene can have diverse effects. Changes within [[regulatory sequence]]s (yellow and blue) can effect [[transcription (genetics)|transcriptional]] and [[Translation (biology)|translational]] regulation of [[gene expression]].]]
[[File:Point mutations-en.png|thumb|right|301px|Point mutations classified by impact on protein]]
[[File:Notable mutations.svg|301px|thumb|right|Selection of disease-causing mutations, in a standard table of the [[genetic code]] of [[amino acid]]s<ref>References for the image are found in Wikimedia Commons page at: [[Commons:File:Notable mutations.svg#References]].</ref>]]

The effect of a mutation on protein sequence depends in part on where in the genome it occurs, especially whether it is in a [[Coding region|coding]] or [[Non-coding DNA|non-coding region]]. Mutations in the non-coding [[regulatory sequence]]s of a gene, such as promoters, enhancers, and silencers, can alter levels of gene expression, but are less likely to alter the protein sequence. Mutations within [[intron]]s and in regions with no known biological function (e.g. [[pseudogene]]s, [[retrotransposon]]s) are generally [[Neutral mutation|neutral]], having no effect on phenotype – though intron mutations could alter the protein product if they affect mRNA splicing.

Mutations that occur in coding regions of the genome are more likely to alter the protein product, and can be categorized by their effect on amino acid sequence:
* A [[frameshift mutation]] is caused by insertion or deletion of a number of nucleotides that is not evenly divisible by three from a DNA sequence. Due to the triplet nature of gene expression by codons, the insertion or deletion can disrupt the reading frame, or the grouping of the codons, resulting in a completely different [[Translation (biology)|translation]] from the original.<ref>{{cite encyclopedia| vauthors = Hogan CM | veditors = Monosson E |encyclopedia=[[Encyclopedia of Earth]]|title=Mutation|url=http://www.eoearth.org/view/article/159530/|access-date=8 October 2015|date=12 October 2010|publisher=Environmental Information Coalition, [[National Council for Science and the Environment]]|location=Washington, D.C.|oclc=72808636|url-status=live|archive-url=https://web.archive.org/web/20151114055631/http://www.eoearth.org/view/article/159530/|archive-date=14 November 2015}}</ref> The earlier in the sequence the deletion or insertion occurs, the more altered the protein produced is. (For example, the code CCU GAC UAC CUA codes for the amino acids proline, aspartic acid, tyrosine, and leucine. If the U in CCU was deleted, the resulting sequence would be CCG ACU ACC UAx, which would instead code for proline, threonine, threonine, and part of another amino acid or perhaps a [[stop codon]] (where the x stands for the following nucleotide).) By contrast, any insertion or deletion that is evenly divisible by three is termed an ''in-frame mutation''.
* A point substitution mutation results in a change in a single nucleotide and can be either synonymous or nonsynonymous.
** A [[synonymous substitution]] replaces a codon with another codon that codes for the same amino acid, so that the produced amino acid sequence is not modified. Synonymous mutations occur due to the [[Degeneracy (biology)|degenerate]] nature of the [[genetic code]]. If this mutation does not result in any phenotypic effects, then it is called [[Silent mutation|silent]], but not all synonymous substitutions are silent. (There can also be silent mutations in nucleotides outside of the coding regions, such as the introns, because the exact nucleotide sequence is not as crucial as it is in the coding regions, but these are not considered synonymous substitutions.)
** A [[nonsynonymous substitution]] replaces a codon with another codon that codes for a different amino acid, so that the produced amino acid sequence is modified. Nonsynonymous substitutions can be classified as nonsense or missense mutations:
*** A [[missense mutation]] changes a nucleotide to cause substitution of a different amino acid. This in turn can render the resulting protein nonfunctional. Such mutations are responsible for diseases such as [[Epidermolysis bullosa]], [[sickle-cell disease]], and [[Superoxide dismutase|SOD1]]-mediated [[Amyotrophic lateral sclerosis|ALS]].<ref>{{cite journal|vauthors=Boillée S, Vande Velde C, Cleveland DW|s2cid=12968143|date=October 2006|title=ALS: a disease of motor neurons and their nonneuronal neighbors|journal=Neuron|volume=52|issue=1|pages=39–59|citeseerx=10.1.1.325.7514|doi=10.1016/j.neuron.2006.09.018|pmid=17015226}}</ref> On the other hand, if a missense mutation occurs in an amino acid codon that results in the use of a different, but chemically similar, amino acid, then sometimes little or no change is rendered in the protein. For example, a change from AAA to AGA will encode [[arginine]], a chemically similar molecule to the intended [[lysine]]. In this latter case the mutation will have little or no effect on phenotype and therefore be [[neutral mutation|neutral]].
*** 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. This sort of mutation has been linked to different diseases, such as [[congenital adrenal hyperplasia]]. (See [[Stop codon]].)