Gene Mutation

• Single gene mutations involve the alteration of a DNA nucleotide sequence in the DNA.
• Gene mutations - Change in the DNA structure of a gene
• Gene mutations are random and can occur in the nucleotide sequence of any chromosome.
• Substitution - These single gene mutations (missense, nonsense and splice-site) are described as point mutations as they change one nucleotide in the DNA sequence of a gene.
• Missense replaces one amino acid codon with another. The altered codon still codes for an amino acid and still makes sense but not the original sense.
• Substitution – Missense

  Sickle cell disease

  Mutation on chromosome 11 alters shape of haemoglobin molecule making it inefficient at transporting oxygen. Red blood cells abnormal/

  sickle shaped.

  Results in sickle cell anaemia if 1 gene affected, or sickle cell disease anaemia if both affected.
• Substitution – Missense

  PKU

  Mutation chromosome 12 causes the production of a non-functional enzyme.
• Nonsense replaces an amino acid codon with a premature stop codon. No amino acid is made and the process stops.

  This leads to a shorter polypeptide chain which is non-functional
• Splice-site: Creating or destroying the codons for exon-intron splicing
• Definition: Mutations are changes in DNA that can result in no protein or altered protein being synthesised.

  Single gene mutations involve the alteration of a DNA nucleotide sequence as a result of:

  • the substitution of nucleotides. (replacing 1 nucleotide with another).
  • insertion of nucleotides.
  • deletion of nucleotides.
• • Missense mutations - result in one amino acid being changed for another. This may result in a non-functional protein or may have little effect on the protein depending on the amino acid that has been changed.

  Example Sickle cell disease.

  • Nonsense mutations - result in premature stop codon being produced which results in a shorter protein. Example Duchenne Muscular dystrophy.
  • Splice site mutations - result in some introns being retained and/or some exons not being included in the mature transcript. Example beta thalassemia.
• The effect of an insertion or deletion of a nucleotide results in frame shift mutations.

  Examples:

  • Cystic fibrosis – Deletion
  • Tay-Sachs disease - Insertion

  Frame shift mutations cause all of the codons and all of the amino acids after the mutation to be changed.

  This has a major effect on the structure of the protein produced.