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Flashcards in DNA & Neuro Disorders Deck (45):
1

2 kinds of neurodegen conditions?

inherited
acquired

2

subset of inherited neurodegen conditions caused by?

unstable repeat expansions

3

what is the most common type of repeat expansion?

trinucleotide
there is also tetranucleotide

4

below the threshold for number of repeat expansions?

stable in both sperm/egg and somatic

5

above the threshold for number of repeat expansions?

unstable and could become toxic

6

what is a characteristic of unstable repeat expansions?

dynamic mutations

7

what is it called when the expansion size increases across generations?

anticipation

8

anticipation of repeat expansions associated with?

greater severity of symptoms

9

what is a proposed mechanism for expansion?

slipped mispairing

10

what is anticipation in terms of unstable repeat expansions for neuro degen diseases?

the expansion size increases across generations

11

unstable repeat expansions are usually what kind of disorders generally?

neurological

12

3 kinds of unstable repeat expansion in terms of coding?

1. non-coding = loss protein function
2. non coding = novel RNA
3. codon = novel toxic protein

13

Huntington's mutation is where in terms of coding?

repeats in codon

14

Friedreich ataxia mutation happens in which coding area?

non-coding leads to loss of protein function

15

what do you see in late onset unstable repeat expansion?

loss of movement control
symptoms worsen
DNA testing

16

3 main features of Huntingtons:

1. motor disorder
2. cognitive disorder
3. psychiatric/emo disorder

17

Huntington's early or late onset?

late normally
small proportion can be <20 due to expansion

18

huntington's inheritred how genetically?

autosomal dominant

19

What repeat in huntington's?

CAG repeat in HTT gene

20

What is HTT?

protein called huntingtin

21

expanded CAG in huntingtin has toxic effect where in brain?

basal ganglia
esp. medium spiny neurons

22

what do you see in brain scans of huntington's?

cerebral atrophy

23

PolyQ-huntingtin cleaved by capsases and make what toxic fragments?

N-terminal fragments

24

huntington's you lose function of normal HTT and also?

mRNA

25

huntington's 27-35 repeats is?

'normal' mutable

26

huntington's >40 repeats?

full penetrance

27

huntington's zone of reduced penetrance is how many?

36-39 repeats

28

huntington's less than 26 repeats?

normal

29

CAG repeats mitigated by?

CCG interruptions

30

huntington's classical testing uses?

radioactive nucleotide tagging and PCR

31

current huntington's testing

fluorescent tagging and fragment analysis

32

spinocereballar ataxias: genetics? onset? features?

autosomal dominant
late onset
progressive cerebellum degen and spinocerebellar tracts

33

spinocereballar ataxias SCA6 causes?

Ca2+ channel protein malformation

34

spinocereballar ataxias SCA 3 called?

Machado-Joseph disease

35

what is Machado Joseph disease?

spinocereballar ataxias SCA3

36

Friedreich ataxia genetics and onset?

autosomal recessive
puberty onset

37

Friedreich ataxia features? 3

1. limb/gait ataxia
2. cardiomyopathy (65%)
3. DM (30%)

38

Friedreich ataxia mutation occurs where in genome?

intron, causes formation of triple helix and inhibits transcription

39

Friedreich ataxia expansion letters?

GAA repeats expansion

40

Friedreich ataxia defect causes what cellularly?

mitochondrial iron accumulation = oxidative damage

41

Friedreich ataxia repeats normal range?

5-33

42

Friedreich ataxia repeats expansion can be?

66-1700!

43

Friedreich ataxia mutable range is?

34-65

44

problems with pre-symptomatic genetic testing?

ethical as there is not really much treatment

45

SCA results interpretations,

REVIEW!!