Mutations | Notion

Molecular lesions that abrogate gene function

(abrogate = officially cancel, annul, or abolish something)

Type	Description
Silent/synonymous	A mutation that does not change the amino acid, often base change in 3rd position of codon
Nonsense	A mutation that results in a stop codon
Missense	A point mutation that changes the amino acid sequence, which in turn may make the protein non-functional
Frameshift	Caused by insertion or deletion of a number of nucleotides which results in the subsequent reading of the DNA 'downstream' being completely wrong

In a Nutshell

Single base substitution and forms stop codon => nonsense
Single base substitution and forms similar codon producing the same amino acid => silent
Single base substitution and changes in an amino acid but similar protein structure and function => missense

A conservative mutation is a specific type of missense mutation where one amino acid is replaced with another amino acid that has similar biochemical characteristics.

Conservative mutations do not alter protein length and may or may not alter secondary structure, protein stability, and protein function.

Splice site mutation

Splice site mutations frequently result in the production of larger proteins with altered function but preserved immune reactivity.

β-thalassaemia: IVS-1-110 (G→A) mutation affecting splicing
Affect mRNA processing rather than coding sequence directly

Deletion

Removal of entire gene
- E.g. alpha-thalassaemia, completement C4A deficiency
Excision of part of a gene -> may cause additional frameshift
- E.g. X-linked muscular dystrophies
Removal of a single codon
- E.g. Delta-F508 (DF508) mutation in cystic fibrosis

Cri-du-chat (cry of the cat) syndrome