Huntingtin Flashcards
Chromosomal position of HTT
4q16
How many exons does the HTT gene span
67 exons
Size of the HTT protein
350kDa
What is the repeat seen in HTT gene
Polymorphic trinucleotide expansion region of CAG
What is the normal HTT expansion
7-35
What conformations does Huntington adopt in its secondary structure
Extended loop, random coil and alpha helices
Where is Huntingtin enriched in the CNS
endoplasmic reticulum, mitochondria and synaptic vesicles
What did Nasir et al (2015) demonstrate
Huntingtin is necessary for embryonic development as knockout mice experienced death at day 8.5
What did McKinstry et al (2014) demonstrate
Huntington requirement for cortical and striatal synapses. Used conditional silencing of Huntington in the developing mouse cortex. Excitatory synapses matured at an accelerated pace but this was last over time and deterioration was seen by week 5
When does Huntington’s disease present?
When there are 36 or more polyglutamine repeats
Is HD autosomal dominant or recessive?
dominant
What is the increase in CAG across generation known as
genetic anticipation and occurs through the male gremline
What are the triad of symptoms
cognitive decline, movement disorder and psychiatric manifestations
where does selective neuronal loss present
GABAergic medium spiny neurones
Loss or gain of function
toxic gain of function
