Huntington Disease: Autosomal Dominant Genetic Disorder

Questions and Answers

50%

Codes for the amino acid glutamine

Excessive signaling of neurons

DNA polymerase can lose track of which CAG it’s on Signup and view all the answers

The repeats become less stable Signup and view all the answers

Higher number of CAG repeats in the protein Signup and view all the answers

Repeat expansion Signup and view all the answers

Because the reasons for this remain unknown Signup and view all the answers

They show 100% penetrance and will have the disease Signup and view all the answers

Because it can accurately predict the development of the disease based on the number of CAG repeats Signup and view all the answers

Study Notes

A rare neurodegenerative disease caused by a repeated sequence of DNA that leads to an abnormal protein formation, resulting in abnormal movements and cognitive problems.
An autosomal dominant genetic disorder, meaning one affected copy of a gene is enough to cause disease.

Typically, the gene called huntingtin or HTT on chromosome 4 contains a triplet repeat of C, A, and G nucleotides 10-35 times in a row.
In people with HD, this repeat goes on for 36 or more times in a row.
The CAG repeat codes for the amino acid glutamine, resulting in 36 or more glutamines in a row in the huntingtin protein.

The mutated protein aggregates within the neuronal cells of the caudate and putamen of the basal ganglia, causing neuronal cell death.
Cell death might be related to excitotoxicity, which is excessive signaling of these neurons, leading to high intracellular calcium.

The expanded CAG repeats affect DNA replication, causing DNA polymerase to lose track of which CAG it's on, resulting in extra CAGs being added.
This expansion occurs during cell divisions, leading to ample opportunities for repeat expansion, making the gene more unstable.

The phenomenon of anticipation means that HD families often show earlier symptom onset with each generation.
Children of a parent with HD can inherit even more CAG repeats than the parent, leading to an earlier age of symptom onset.
Repeat expansion occurs more in the production of sperm than eggs, resulting in anticipation and new disease alleles when the father is the affected parent.

A person with 40+ repeats shows 100% penetrance and will have the disease.
People with 36-39 repeats can show reduced penetrance, with some having symptoms while others may not.
The test for HD, which counts the number of CAG repeats, is effective in determining whether HD will develop in an at-risk individual.