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Flashcards in genetics Deck (16)
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1
Q

explain “anticipation” in regards to unstable repeat expansions

A

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

2
Q

where are the unstable repeat expansions in Huntington disease and Friedreich ataxia

A

HTT - in a codon for the HTT protein

Friedreich ataxia - in an intron

3
Q

what is the inheritance of HTT and Friedreich ataxia

A

HTT - autosomal dominant

Friedreich ataxia - autosomal recessive

4
Q

main features of HTT disease

A

movement/motor disorder
cognitive, psychiatric disorder
PROGRESSIVE NEURODEGENERATION

5
Q

what is the unstable repeat expansion in HTT disease

A

CAG repeat in exon 1 of HTT gene found on chromosome 4 (CAG codes for glutamine)

6
Q

What is the normal role of HTT protein

A

roles in transcription, intracellular transport of other molecules, intracellular signalling and metabolism and in reducing apoptosis

7
Q

which area of the brain does the polyQ-HTT protein affect first

A

the medium spiny neurons of the basal ganglia

8
Q

what do you see on CT scan/MRI scan of a HTT brain

A

atrophy of the regions that would be the basal ganglia - fluid filled regions

9
Q
how many CAG repeats do you need to be:
normal:
normal but mutable:
reduced penetrance
affected:
A

normal less than 26
normal but mutable 27-35
reduced penetrance 36-39
affected 40 or more

10
Q

what is the inheritance of spinocerebellar ataxias

A

autosomal dominant

11
Q

what are the main features of spinocerebellar ataxia

A

progressive degeneration of:

  • cerebellum
  • brain stem
  • spinocerebllar tracts
12
Q

what is the age of onset of HTT and Friedreich ataxia

A

HTT - 30-40

Friedreich ataxia - around puberty

13
Q

main features of Friedreich ataxia

A

progressive limb and gait ataxia
cardiomyopathy
diabetes mellitus

14
Q

what is the unstable repeat expansion of Friedreich ataxia

A

GAA repeat intron 1 of in frataxin (FXN) gene on chromosome 9

15
Q

what does the mutation of intron 1 in Friedreich ataxia cause

A

abnormal DNA secondary structure or induces heterochromatin –> reduced protein prodction

16
Q

compare the number of repeats needed for penetrance between HTT and Friedreich ataxia

A

HTT - >40

Friedreich ataxia - may need 100s-1000