The Huntingtin gene, also called HD (Huntington disease) gene, or the IT15 ("interesting transcript 15") gene codes for a 348 kDa protein called huntingtin protein. The exact function of this protein is not known, but it plays an important role in nerve cells. Within cells, huntingtin may be involved in signaling, transporting materials, binding proteins and other structures, and protecting against programmed cell death (apoptosis). The huntingtin protein is required for normal development before birth. It is expressed in many tissues in the body, with the highest levels of expression seen in the brain.

The 5' end of the HD gene has a sequence of 3 DNA bases, cytosine-adenine-guanosine (CAG), coding for the amino acid glutamine, that is repeated multiple times. This region is called a trinucleotide repeat. Normal persons have a CAG repeat count of between 7 and 35 repeats.

The HD gene is located on the short (p) arm of chromosome 4 at position 16.3, from base pair 3,113,411 to base pair 3,282,655.

Associated Disorders

Huntington's disease is caused by a mutation in the Huntingtin gene, where the CAG repeats more than 35 times and is unstable. These expanded repeats lead to production of a huntingtin protein that contains an abnormal number of glutamines at the N-terminal. This makes it part of a class of neurodegenerative disorders known as trinucleotide repeat disorders or polyglutamine disorders.

Enzymes in the cell often cut this elongated protein into fragments. The protein fragments form abnormal clumps inside nerve cells and may attract other, normal proteins into the clumps. These nerve cells do not function properly and ultimately die. This process is particularly likely to occur in the striatum (a part of the brain that coordinates movement) primarily, and the frontal cortex (a part of the brain that controls thinking and emotions).

People with 36 to 40 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with more than 40 repeats will develop the disorder during a normal lifetime. When there are more than 100 CAG repeats, the person develops a severe form of HD known as Juvenile HD. Therefore, the number of CAG (the sequence coding for the amino acid glutamine) repeats influences the age of onset of the disease. No case of HD has been diagnosed with a count less than 36.^[1]

As the altered gene is passed from one generation to the next, the size of the CAG repeat expansion can change; it often increases in size, especially when it is inherited from the father. People with 27 to 35 CAG repeats have not been reported to develop the disorder, but their children are at risk of having the disease if the repeat expansion increases.

References

External links

• GeneCard
• iHOP

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