Genetic Mutations Lecture Notes

Central Dogma of Molecular Biology

• DNA to RNA to Protein:
  • DNA nucleotides → RNA (transcription) → Protein (translation)
  • DNA nucleotides are transcribed to complementary RNA forms
  • RNA codons (groups of three nucleotides) code for specific amino acids

Genetic Mutations

• Definition: Mistakes in a cell's DNA leading to abnormal protein production
• Impact: Mutations in DNA affect RNA sequence and the resulting protein

Types of Genetic Mutations

Point Mutations

• Description: One DNA base is replaced with another
• Example: CTC (DNA) → GAG (RNA) → Glutamate (Protein)
  • Mutation: Thymine replaced with Adenine
  • Result: Changed amino acid

Frame-Shift Mutations

• Description: Addition or deletion of a DNA base changes the reading frame of RNA
• Example: CTC + extra Cytosine (blue)
  • Result: Additional Guanine in mRNA
  • Effect: Changed reading frame, leading to different amino acids
  • Impact: Larger effect on the final protein than point mutations

Non-Sense and Missense Mutations

• Non-Sense Mutations:
  • DNA mutation leads to RNA sequence becoming a stop codon
  • Effect: Potentially large sections of the protein chopped off
• Missense Mutations:
  • DNA mutation changes one amino acid to another
  • Types of Missense Mutations:
    • Silent Mutations: No effect on the protein (multiple codons code for same amino acid)
    • Conservative Mutations: New amino acid is of the same type as the original
    • Nonconservative Mutations: New amino acid is of a different type from the original

Example: Sickle Cell Disease

• Disorder: Hemoglobin mutated to a less active form (HbS)
• Cause: Single glutamate residue is converted to a valine residue
• Classification:
  • Point mutation (single DNA base affected)
  • Nonconservative missense mutation (glutamate swapped for valine, different types of amino acids)

Summary

• Mutations originate at the DNA level but show effects on the protein level
• Classification:
  • Based on DNA impact: Point and Frame-Shift Mutations
  • Based on Protein impact: Missense and Non-Sense Mutations