Cag trinucleotide repeat expansion

Definition

CAG trinucleotide repeat expansion refers to a genetic mutation where the DNA sequence 'CAG' is repeated multiple times in succession, leading to the production of an elongated polyglutamine (polyQ) tract in proteins. This phenomenon is particularly significant in certain neurodegenerative disorders, where the accumulation of abnormally long polyQ proteins can disrupt cellular function and lead to neurodegeneration, contributing to the pathogenesis of diseases such as Huntington's disease.

5 Must Know Facts For Your Next Test

1. CAG repeats can be stable at low numbers but become unstable and expand in subsequent generations, a phenomenon known as genetic anticipation.
2. The threshold for CAG repeats varies across different genes; for instance, more than 35 repeats in the HTT gene typically leads to Huntington's disease.
3. PolyQ proteins with expanded CAG repeats can misfold and aggregate, causing cellular toxicity and disrupting normal cellular functions.
4. CAG repeat expansions are not only found in Huntington's disease but also in other disorders like spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy.
5. Research is ongoing to develop therapies aimed at reducing the impact of CAG repeat expansions, including gene silencing techniques and small molecule drugs.

Review Questions

• What is the role of CAG trinucleotide repeat expansion in the development of Huntington's disease, and how does it affect protein function?
  • CAG trinucleotide repeat expansion leads to the production of an abnormally long polyglutamine tract in the huntingtin protein. This elongated protein tends to misfold and aggregate within neurons, disrupting cellular processes and ultimately causing neuronal cell death. As a result, individuals with Huntington's disease experience progressive motor dysfunction, cognitive decline, and psychiatric symptoms linked to this cellular toxicity.
• Discuss the implications of genetic anticipation associated with CAG repeat expansions across generations.
  • Genetic anticipation refers to the phenomenon where a genetic disorder exhibits an earlier onset and increased severity in successive generations. In the case of CAG repeat expansions, this occurs because the number of repeats may increase when passed from parent to offspring. As a result, children may develop conditions like Huntington's disease at a younger age than their parents did, often with more severe symptoms due to a higher number of CAG repeats.
• Evaluate potential therapeutic strategies targeting CAG trinucleotide repeat expansions in neurodegenerative disorders, and their effectiveness based on current research.
  • Current research is focused on several therapeutic strategies aimed at mitigating the effects of CAG trinucleotide repeat expansions. These include gene silencing techniques that target the mRNA produced from mutated genes, thus reducing the production of toxic proteins. Additionally, small molecule drugs that enhance protein folding or promote degradation of aggregated proteins are being explored. While early studies have shown promise, more extensive clinical trials are needed to determine their effectiveness and safety for long-term use in patients with conditions like Huntington's disease.

Related terms

Huntington's disease: A hereditary neurodegenerative disorder characterized by the progressive breakdown of nerve cells in the brain, often associated with CAG repeat expansions in the HTT gene.

Polyglutamine diseases: A group of disorders caused by CAG repeat expansions in various genes, leading to neurodegeneration and motor dysfunction.

Neurodegeneration: The progressive loss of structure or function of neurons, often resulting in cognitive decline and movement disorders.