What is the pathogenesis of Huntington's?
Expanded CAG repeated in hungtingtin protein that is toxic to basal ganglia cells > atropy eventually effects the whole brain
What are the genetics for Friedreich ataxia?
How many repeats do you need to have to transmit Huntington's to offspring?
What is the mean age of onset for Huntington's?
Where are the pathological effects of Huntington's seen?
The basal ganglia, particularly the striatum
What happens at the biochemical level in Friedreich ataxia?
The frataxin protein isn't produced.
Causing iron accumulation in mitochondria causing oxidative damage
What test is used for diagnosing Huntington's?
PCR - fragment analysis
What are the symptoms of Huntington's?
Which type of Spinocerebellar ataxia is most prevalent in Australia?
SCA3 (aka Machado-Joseph disease)
What is the usual cause of death in Friedreich ataxia?
How can the repeats effect the protein/RNA/DNA?
1. Cause loss of protein
2. Cause novel properties to RNA
3. Cause novel properties to protein
What are the genetics of Huntington's and Spinocerebellar ataxia?
How many bases are usually contained in the repeats?
How many repeats must you have for Huntington's to present?
What does anticipation refer to in the context of Huntington's?
The more repeat sequences the more severe the disease is and the early the onset is.
T/F Just the basal ganglia are effected in a Huntington's brain
False, eventually the whole brain is atropied
What effect do the repeats have at the protein level in Huntington's?
Confers novel properties to the protein
What are some characteristics of neurodegenerative diseases caused by repeat expansions?
Loss of movement control
Variable and overlapping clinical presentation
Symptoms worsen over time
DNA testing can aid diagnosis
What is the possible mechanism for insertion of repeats called?
T/F Repeat regions are always abnormal.
False, they are present normally too