DNA Testing: Neurodegenerative Disorders Flashcards
What are unstable repeat expansions? what are the most common?
Repetitions of >3 nucleotides in tandem
Trinucleotides Repeats
How is it possible for people with fragile X syndrome to develop symptoms when they have a healthy # of repeats?
Because the mRNA gains toxic properties
Define: Anticipation
Expansion of repeats in the following generations
How is the process of expansion thought to occur?
because during replication of the DNA one of the repeats comes off the template strand and other downstream attaches to that site and then normal replication continues to occur
What inheritance pattern shows Huntington’s Disease
Autosomal Dominant
Huntington’s Disease age of presentation
Adult
at the beggining of the pathology of Huntington’s Disease there is increased movement that progressively disappears T/F
T
Where is the repeat found in Huntington’s Disease?
what is the name of the gene?
What does the repeat code for?
CAG repeat in exon 1 of the
gene hungtintin in chromosome 4
Poly-glutamine tail (PolyQ)
what cells are affected for the motor changes seen in Huntington’s Disease
Medium Spiny Neurons of the basal Ganglia
why is the polyQ tail of the gene problematic if too long
can induce apoptosis due to deficient cleaving by caspases that produce N terminals that can aggregate into plaques (more oxidative stress and excitotoxicity)
What are the gene categories found in Huntington’s Disease?
Normal (40)
What inheritance pattern shows Spinocerebellar ataxias
Autosomal Dominant (late onset)
In Spinocerebellar ataxia SC A6 what is the damaged protein
Ca+2 Channel
in SCA6 where is the gene located and how many repeats required to get the condition
19
In Fredreich Ataxia what is the inheritance pattern
Autosomal Recessive
In Fredreich Ataxia when is the onset
puberty
Fredreich Ataxia symptoms and signs
Progressive limb ataxia, cardiomyopathy, diabetes mellitus
In Fredreich Ataxia where is the repeat located
What is the name of the gene? what is its function?
In an intron
FXN located in chromosome 9 (ion exchanger in mitochondria)
In Fredreich Ataxia how many repeats required for developing symptoms
66-1700
Repeats form triple helix that inhibits transcription of the gene (GAA)
Symptoms can also be developed by inactivating point mutations
Is genetic testing of children recommended?
No as there is nothing to be done
Wat is the role of the protein hungtintin?
transcription factor for other genes
