Introduction to Repeat Expansions

• Definition: Repeat expansions refer to the abnormal increase in the number of tandem nucleotide repeats in specific regions of the genome.
  • Examples: CAG, CGG, CTG, GAA repeats.

  Key Concepts

  1. Mechanism of Repeat Expansion

     • Replication Slippage:
       • DNA polymerase dissociates temporarily, leading to misalignment and addition of extra repeats.
     • Mismatch Repair Defects:
       • Errors during repair of DNA loops in repetitive regions propagate repeats.
     • Recombination Errors:
       • Unequal crossing over during meiosis adds repeats to one allele.

  2. Thresholds for Pathogenicity

     • Premutation: Repeats below pathogenic thresholds but prone to further expansion.
     • Full Mutation: Repeats exceed critical thresholds, impairing gene function.
     • Disease-specific thresholds:
       • Huntington’s disease: >40 CAG repeats.
       • Fragile X syndrome: >200 CGG repeats.

  3. Types of Repeat Expansions

     • Coding Region Repeats:
       • Polyglutamine diseases (e.g., Huntington’s disease) result in toxic protein aggregates.
     • Non-Coding Region Repeats:
       • Disrupt transcription, splicing, or RNA function (e.g., Fragile X, Myotonic Dystrophy).

  Login to Read More

  Information

  Keywords: Repeat Expansions, Huntington's Disease, Fragile X Syndrome, Spinocerebellar Ataxias, Friedrich's Ataxia, Myotonic Dystrophy

  Published:29 December 2024 Last Updated:31 December 2024