genetics Flashcards
explain “anticipation” in regards to unstable repeat expansions
when the repeat is passed down in generations the number of repeats increases (anticipation) and the age of onset decreases and the disease severity increases
where are the unstable repeat expansions in Huntington disease and Friedreich ataxia
HTT - in a codon for the HTT protein
Friedreich ataxia - in an intron
what is the inheritance of HTT and Friedreich ataxia
HTT - autosomal dominant
Friedreich ataxia - autosomal recessive
main features of HTT disease
movement/motor disorder
cognitive, psychiatric disorder
PROGRESSIVE NEURODEGENERATION
what is the unstable repeat expansion in HTT disease
CAG repeat in exon 1 of HTT gene found on chromosome 4 (CAG codes for glutamine)
What is the normal role of HTT protein
roles in transcription, intracellular transport of other molecules, intracellular signalling and metabolism and in reducing apoptosis
which area of the brain does the polyQ-HTT protein affect first
the medium spiny neurons of the basal ganglia
what do you see on CT scan/MRI scan of a HTT brain
atrophy of the regions that would be the basal ganglia - fluid filled regions
how many CAG repeats do you need to be: normal: normal but mutable: reduced penetrance affected:
normal less than 26
normal but mutable 27-35
reduced penetrance 36-39
affected 40 or more
what is the inheritance of spinocerebellar ataxias
autosomal dominant
what are the main features of spinocerebellar ataxia
progressive degeneration of:
- cerebellum
- brain stem
- spinocerebllar tracts
what is the age of onset of HTT and Friedreich ataxia
HTT - 30-40
Friedreich ataxia - around puberty
main features of Friedreich ataxia
progressive limb and gait ataxia
cardiomyopathy
diabetes mellitus
what is the unstable repeat expansion of Friedreich ataxia
GAA repeat intron 1 of in frataxin (FXN) gene on chromosome 9
what does the mutation of intron 1 in Friedreich ataxia cause
abnormal DNA secondary structure or induces heterochromatin –> reduced protein prodction
