Huntingtons Disease

Question 1

How many individuals does Huntington’s disease affect?

Answer 1

Huntington’s affects approximately 5-10 individuals per 100,000 in Caucasian populations

Question 2

Mutations in what gene result in Huntington’s disease?

Answer 2

Mutations in the HTT gene encoding the huntingtin protein cause Huntington’s disease

Question 3

In individuals with Huntington’s, the HTT gene frequently contains an abnormal number of ___________ residues

Answer 3

Glutamine. Individuals with Huntington’s disease have an expanded poly-glutamine (poly-Q) stretch within the HTT gene

Question 4

Huntington's disease is inherited in what fashion?:
A) Autosomal dominant
B) Autosomal recessive
C) X-linked dominant 
D) X-linked recessive

Answer 4

A) Autosomal Dominant

Question 5

What trinucleotide repeat sequence is extended in individuals with Huntington’s?

Answer 5

The trinucleotide CAG is repeated many times in the HTT gene of individuals with Huntington’s disease

Question 6

What is the normal length of the poly-glutamine (poly-Q) repeat in individuals who do not suffer from Huntington’s disease.

Answer 6

In unaffected individuals, the number of glutamine residues ranges from 7 to 36.

Question 7

What length poly-Q repeat is associated with Huntington’s disease?

Answer 7

Repeat sequences longer than 36 residues are associated with Huntington’s disease.

Question 8

Insoluble huntingtin aggregates within neurons have traditionally been assumed to be highly detrimental to neuronal survival. Briefly describe how Huntingtin aggregates may be beneficial to neuronal survival.

Answer 8

• Insoluble aggregates of Huntingtin may form as a neuroprotective mechanism
• Studies have indicated that neurons with fewer aggregates are more susceptible to degeneration than neurons with insoluble Huntingtin aggregates.

Question 9

What treatments for Huntington’s disease are currently available.

Answer 9

Current treatments focus on reducing and managing the symptoms of the disease and include:

• Antidepressants
• Medication reducing involuntary movements

Question 10

What cellular process can soluble aggregates of Huntingtin impair?

Answer 10

Insoluble Huntingtin aggregates can impair the functioning of the 26s proteasome, impairing protein degradation and turnover within the cell.