6.2.6—Gene mutations

A gene mutation is a change in the DNA base or base-pair sequence of a gene. It changes the stored sequence information; its biological consequence must be traced rather than assumed from the word “mutation”.

• Substitution: one base pair is replaced by another. This may leave the encoded amino acid unchanged or may alter a codon, depending on the position and the new base.
• Insertion: one or more base pairs are added to the sequence. The addition can change how downstream bases are grouped into codons, especially when the number added is not a multiple of three.
• Deletion: one or more base pairs are removed. Like an insertion, a non-triplet change can shift the downstream reading frame; a triplet-sized change can have a different reach.
• Consequence boundary: DNA change → possible mRNA/codon change → possible amino-acid or polypeptide change. The result depends on where the change occurs, how many bases are affected, and whether the relevant sequence is read or expressed.

A mutation matters through the expression chain, not by definition: a DNA sequence change may be silent, may alter one codon, or may regroup many downstream codons if the reading frame changes. A change outside the relevant coding information can have a different outcome, so mutation type alone is not enough to predict a polypeptide or phenotype.

Substitution, insertion and deletion describe different edits to DNA; they do not automatically describe the final protein effect. Not every mutation is harmful or changes an amino acid, and not every insertion/deletion causes a frameshift. Do not name a disease or phenotype without evidence for the specific sequence and expression context.