Genetic Mutations

A mutation is an alteration in the DNA sequence. There are many types of DNA mutations: point mutations, deletions, insertions, frame shifts, duplications, and trinucleotide repeat expansions.

Mutation Definitions

• Point mutation - Substitution of one nucleotide for another within a gene.
  • Missense mutation: point mutation resulting in the exchange of one amino acid for another in the final protein product.
  • Nonsense mutation: point mutation resulting in a truncated protein product by creating a premature stop codon.
  • Splice mutation: point mutation that alters the protein product by preventing normal post-transcriptional processing of RNA.
  • Examples include: Charcot-Marie Tooth Type 1B, Presenilin-1, Familial Amyloidotic Polyneuropathy
• Deletion/Insertion - A loss/gain of DNA sequence that can range from a single base pair within a gene to a large part of the chromosome.
  • Examples of disorders caused by deletions include: Facioscapulohumeral Muscular Dystrophy, Spinal Muscular Atrophy
  • A deletion or insertion may cause a Frame Shift mutation: a change in the reading frame of the gene (this occurs if the number of base pairs in the deletion or insertion is not a multiple of three). In most cases, the altered reading frame results in a truncated or elongated protein. Duchenne Muscular Dystrophy may be caused by a frame shift mutation.
• Deletion/Duplication - The repetition or deletion of a gene during meiosis due to unequal crossing over or mispairing of chromosomes/sister chromatids.
  • Example of a duplication: Charcot-Marie-Tooth Type 1A is caused by a duplication of the Peripheral Myelin Protein-22 gene (PMP-22).
  • Example of a deletion: Hereditary Neuropathy with Liability to Pressure Palsy (HNPP) is caused by a deletion of the PMP-22 gene.
• Trinucleotide repeat expansion - Three nucleotides, such as CAG, CTG or GAA, are tandemly repeated an abnormal number of times within a gene. The genetic transmission of trinucleotide repeat expansion disorders within families may show a pattern of increasing severity and earlier age of onset; this phenomenon is called anticipation and is the result of an increase in the expansion size.
  • Examples include: Huntington's Disease, Myotonic Dystrophy