D1.3 Mutation and Gene Editing

Mutation Definition

A mutation occurs when the sequence of DNA bases is altered.

3 main types of gene mutation

Substitution:

• one base in coding sequence is replaced by another.

• can happen by chemical changes to bases or by mispairing during replication.

Insertion:

• a nucleotide is inserted, so extra base in the sequence.

• more major as a break is needed in the sugar phosphate backbone.

Deletion:

• a nucleotide is removed so there is one less base in the sequence.

• this requires two breaks in the backbone.

Consequences of base substitution:

Same-sense

Nonsense

Mis-sense

Mostly neutral or deleterious and in some cases lethal. In non-coding DNA, they are unlikely to have any effect – only changes to coding sequences can affect amino acid sequences of polypeptides

Same-sense

Same-sense mutations change one codon for an amino acid into another codon for same amino acid. Possible due to redundancy of genetic code. Eg. a change from AGC to AGT still codes for serine. No effect on phenotype

Nonsense

Nonsense mutation change a codon for an amino acid into a stop codon (ATT, ATC or ACT). So translation is terminated before polypeptide is complete. Doesn’t function properly.

Mis-sense

Mis-sense mutations alter one amino acid in the sequence in a polypeptide. May not have much effect if new amino acid has similar structure + chemical prop. But can be lethal, cause of many genetic diseases like sickle cell

Mis-sense further info

When DNA from individual humans is sequenced, large numbers of historical base substitutions are found.

Known as single-nucleotide polymorphisms (SNPs).

Can occur in non-coding regions of DNA.

Presence of some SNPs is associated with certain diseases.

These correlations allow scientists to determine an individual’s genetic predisposition to developing a disease.