Gene Mutations

• Gene mutations


  Alteration of a gene (allele) sequence of nucleotides (bases)
• Types of gene mutation

  • Insertion
  • Deletion
  • Substitutions
• Insertion


  1. A nucleotide is added into the normal DNA sequence by mistake

  2. Changes the way the sequence is read by RNA polymerase

  3. Results in a change in the primary structure of a protein coded for by that gene
• Frame shift


  The change in the way the gene is read
• Frame shift affects the secondary, tertiary and quaternary structures and may result in a non functional protein
• Deletion


  1. One or more nucleotides are lost from the normal DNA sequence

  2. Causes a frame shift

  3. Proteins produced are often non functional
• Types of substitution


  • Nonsense mutation
  • Missense mutation
  • Silent mutation
• Nonsense mutation


  The substitution results in the formation of a stop codon that marks the termination of a polypeptide chain
• Missense mutation


  The change results in a different amino acid being coded for
• Silent mutation


  Substitution results in a different base occurring but forms a triplet that codes for the same amino acid
• Albinism


  • Mutation of the TYR gene (mutation on chromosome 11)
  • Rare inherited condition in mammals
  • Block in the biochemical pathway by which the skin pigment melanin is produced
  • Mutated allele (on chromosome 11) is recessive
  • Enzyme tyrosinase required for melanin production is non-functional
• Melanin production


  1. Tyrosine -> DOPA -> dopaquinone -> melanin

  2. Tyrosinase enzyme involved in all stages
• Sickle cell anaemia


  • Mutation of the HBB gene (mutation on chromosome 11)
  • Inherited form of anaemia
  • Change in the base sequence of the triplet coding for one amino acid out of the 146 in the beta chain
  • Substitution of valine for glutamic acid
  • Sickle cell haemoglobin crystallises at low oxygen concentrations distorting shape of red blood cell that can block capillaries
  • Less oxygen delivered to tissues causing tiredness and weakness
  • Heterozygotes have the sickle cell trait, roughly half of their cells are normal
• Sickle cell trait


  Heterozygotes quickly get tired on the slightest exertion
• Lack of tissue oxygen can cause attacks of sudden, severe pain, called pain crises
• Over a lifetime, SCD can harm a person's spleen, brain, eyes, lungs, liver, heart, kidneys, penis, joints, bones, or skin
• Homozygous individuals die due to inadequate supply of blood to tissues, high blood pressure, heart attacks etc
• Huntington's disease


  • Mutation of HTT gene on chromosome 4
  • Inherited condition that damages certain nerve cells in the brain
  • Brain damage gets progressively worse over time and can affect movement, cognition and behaviour
  • Caused by a mutation which forms a dominant allele (on chromosome 4)
  • Huntington allele contains several repeats of the base sequence CAG, which codes for the amino acid glutamine
  • Gene with more than 36 CAG repeats produces a protein that does not fold properly and does not function
  • Symptoms usually first appear between the ages of 30 & 45 years
  • No treatment, progressive and always fatal
• Affected people have the Huntington allele


  They have a 50% chance of passing it on to their children