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DNA Mutations
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DNA Mutations

TYPES OF MUTATIONS
Substitution: single nucleotide replaced
  • Point mutations
  • Nonsense mutation: generates stop codon
  • Missense mutation: generates incorrect amino acid
  • Silent mutation: generates same amino acid
Deletion: single nucleotide removed
  • Frame-shift mutation
Insertion: single nucleotide inserted
  • Frame-shift mutation
FIDELITY OF REPLICATION
  • Frequency of replication errors very low (1 in 10^9 nucleotides added)
  • DNA polymerase increases fidelity:
i. Selects for correct nucleotide ii. Proofreads (3' to 5' exonuclease)
CLINICAL CORRELATION
Sickle-cell anemia
  • Missense mutation (adenine to thymine) changes 3D structure of hemoglobin beta-subunit
  • Produces valine instead of glutamate
  • Results in sickle-shaped red blood cell instead of biconcave
  • Confers malaria-resistance: parasite cannot grow in mutated hemoglobin