Trinucleotide repeat expansion

Trinucleotide repeat expansion is a type of genetic mutation that involves the repetition of a sequence of three nucleotides (trinucleotide) in the DNA of a gene. This expansion can lead to various genetic disorders, depending on the gene affected and the number of repeats.

Mechanism

Trinucleotide repeat expansions occur when the number of repeats of a specific trinucleotide sequence increases beyond a normal range. This can happen during DNA replication when the DNA polymerase "slips" and adds extra repeats. The most common trinucleotide repeats are CAG, CTG, CGG, and GAA.

Associated Disorders

Trinucleotide repeat expansions are associated with several genetic disorders. Some of the most well-known include:

• Huntington's disease: Caused by an expansion of CAG repeats in the HTT gene.
• Fragile X syndrome: Results from an expansion of CGG repeats in the FMR1 gene.
• Myotonic dystrophy: Involves CTG repeat expansions in the DMPK gene.

Pathophysiology

The expansion of trinucleotide repeats can disrupt normal gene function in several ways. In some cases, the expanded repeats lead to the production of abnormal proteins that aggregate and cause cellular damage. In other cases, the expansion affects gene expression, leading to a loss of function.

Diagnosis

Diagnosis of disorders caused by trinucleotide repeat expansions typically involves genetic testing. Techniques such as polymerase chain reaction (PCR) and Southern blotting are used to determine the number of repeats in a gene.

Treatment

Currently, there are no cures for disorders caused by trinucleotide repeat expansions. Treatment focuses on managing symptoms and may include medications, physical therapy, and supportive care.

Research

Ongoing research aims to better understand the mechanisms of trinucleotide repeat expansions and develop targeted therapies. Gene editing technologies, such as CRISPR-Cas9, are being explored as potential treatments.

Related pages

• Genetic mutation
• DNA replication
• Huntington's disease
• Fragile X syndrome

References

Diagram illustrating the structure of DNA and the location of trinucleotide repeats.