Type of DNA Mutations

Silent 

• Exchange of one base for another results in same amino acid
  • often an alteration in 3rd position of codon
    • tRNA wobble
• No change in protein function

Missense 

• Exchange of one base for another results in changed amino acid 
  • transversion → exchanges a purine to a pyrimidine or a pyrimidine to a purine
    • e.g., C → A or G → T
  • transition → exchanges a purine for another purine or a pyrimidine to another pyrimidine
    • e.g., A → G or C → T
• Variable change in protein function
  • if the new amino acid is similar to old (leu → ile) the protein will most likely function the same
  • if the new amino acid is different (glu → val) the protein folding/stability will likely be affected
• e.g., sickle-cell anemia 
• glu → val mutation in β-globin gene

Nonsense 

• Exchange of one base for another results in a stop codon 
• Loss of function mutation as peptide is truncated

Frameshift 

• Deletion or addition of 1 or 2 bases resulting in misreading of all nucleotides downstream
• Loss of function mutation as peptide is completely different

Large Segment Deletion

• Unequal crossover at meiosis results in loss of large segment of DNA
• Loss of function mutation
• e.g., α-thalassemia 
• deletion of α-globin gene 

Change at splice site

• Alteration in base sequence at mRNA splicing site results in altered splicing
  • can remove parts of exon
  • can leave parts of intron
• Variable effect on protein function as number of spliced amino acids varies
• e.g., β-thalassemia

Triplet repeat expansion

• Expansion of short nucleotide sequence results in longer polypeptide
  • can be in coding or noncoding region
• Addition of amino acids affects protein structure/folding and affects function
• Disease display anticipation
  • earlier disease onset in successive generations
• e.g., myotonic dystrophy, Huntington’s disease, and Fragile X

In-frame 

• In-frame mutations