CAG repeats

CAG Repeats

CAG repeats are sequences of DNA in which the nucleotides cytosine (C), adenine (A), and guanine (G) are repeated multiple times in tandem. These repeats are found in various locations throughout the human genome and can have significant implications for genetic function and disease.

Structure and Function

CAG repeats are a type of trinucleotide repeat, which means they consist of three nucleotides repeated in sequence. The number of repeats can vary between individuals and can be stable or unstable during cell division. In some genes, CAG repeats are located within coding regions and are translated into polyglutamine tracts in proteins, as the codon CAG codes for the amino acid glutamine.

Genetic Disorders

CAG repeat expansions are associated with several genetic disorders, most notably the group of diseases known as polyglutamine (polyQ) diseases. These include:

• Huntington's disease: An autosomal dominant neurodegenerative disorder caused by an expansion of CAG repeats in the HTT gene. Individuals with more than 36 repeats typically develop symptoms of the disease.
• Spinocerebellar ataxia: A group of hereditary ataxias that are characterized by progressive incoordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Several types of spinocerebellar ataxia are caused by CAG repeat expansions.
• Kennedy's disease: Also known as spinal and bulbar muscular atrophy (SBMA), this X-linked recessive disorder is caused by CAG repeat expansions in the androgen receptor gene.

Mechanism of Disease

The expansion of CAG repeats in certain genes can lead to the production of proteins with abnormally long polyglutamine tracts. These proteins tend to misfold and aggregate, forming insoluble inclusions in neurons and other cells. The accumulation of these aggregates is toxic and leads to cellular dysfunction and death, contributing to the symptoms of the associated diseases.

Genetic Testing and Counseling

Genetic testing can identify the number of CAG repeats in specific genes, which is useful for diagnosing diseases like Huntington's disease and for assessing the risk in family members. Genetic counseling is recommended for individuals undergoing testing to understand the implications of the results.

Also see

• Trinucleotide repeat disorder
• Genetic anticipation
• Polyglutamine disease
• Neurodegenerative disease