DNA & Neuro Disorders

Question 1

2 kinds of neurodegen conditions?

Answer 1

inherited

acquired

Question 2

subset of inherited neurodegen conditions caused by?

Answer 2

unstable repeat expansions

Question 3

what is the most common type of repeat expansion?

Answer 3

trinucleotide

there is also tetranucleotide

Question 4

below the threshold for number of repeat expansions?

Answer 4

stable in both sperm/egg and somatic

Question 5

above the threshold for number of repeat expansions?

Answer 5

unstable and could become toxic

Question 6

what is a characteristic of unstable repeat expansions?

Answer 6

dynamic mutations

Question 7

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

Answer 7

anticipation

Question 8

anticipation of repeat expansions associated with?

Answer 8

greater severity of symptoms

Question 9

what is a proposed mechanism for expansion?

Answer 9

slipped mispairing

Question 10

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

Answer 10

the expansion size increases across generations

Question 11

unstable repeat expansions are usually what kind of disorders generally?

Answer 11

neurological

Question 12

3 kinds of unstable repeat expansion in terms of coding?

Answer 12

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

Question 13

Huntington’s mutation is where in terms of coding?

Answer 13

repeats in codon

Question 14

Friedreich ataxia mutation happens in which coding area?

Answer 14

non-coding leads to loss of protein function

Question 15

what do you see in late onset unstable repeat expansion?

Answer 15

loss of movement control
symptoms worsen
DNA testing

Question 16

3 main features of Huntingtons:

Answer 16

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

Question 17

Huntington’s early or late onset?

Answer 17

late normally

small proportion can be <20 due to expansion

Question 18

huntington’s inheritred how genetically?

Answer 18

autosomal dominant

Question 19

What repeat in huntington’s?

Answer 19

CAG repeat in HTT gene

Question 20

What is HTT?

Answer 20

protein called huntingtin

Question 21

expanded CAG in huntingtin has toxic effect where in brain?

Answer 21

basal ganglia

esp. medium spiny neurons

Question 22

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

Answer 22

cerebral atrophy

Question 23

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

Answer 23

N-terminal fragments

Question 24

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

Answer 24

mRNA

Question 25

huntington's 27-35 repeats is?

Answer 25

'normal' mutable

Question 26

huntington's >40 repeats?

Answer 26

full penetrance

Question 27

huntington's zone of reduced penetrance is how many?

Answer 27

36-39 repeats

Question 28

huntington's less than 26 repeats?

Answer 28

normal

Question 29

CAG repeats mitigated by?

Answer 29

CCG interruptions

Question 30

huntington's classical testing uses?

Answer 30

radioactive nucleotide tagging and PCR

Question 31

current huntington's testing

Answer 31

fluorescent tagging and fragment analysis

Question 32

spinocereballar ataxias: genetics? onset? features?

Answer 32

autosomal dominant late onset progressive cerebellum degen and spinocerebellar tracts

Question 33

spinocereballar ataxias SCA6 causes?

Answer 33

Ca2+ channel protein malformation

Question 34

spinocereballar ataxias SCA 3 called?

Answer 34

Machado-Joseph disease

Question 35

what is Machado Joseph disease?

Answer 35

spinocereballar ataxias SCA3

Question 36

Friedreich ataxia genetics and onset?

Answer 36

autosomal recessive | puberty onset

Question 37

Friedreich ataxia features? 3

Answer 37

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

Question 38

Friedreich ataxia mutation occurs where in genome?

Answer 38

intron, causes formation of triple helix and inhibits transcription

Question 39

Friedreich ataxia expansion letters?

Answer 39

GAA repeats expansion

Question 40

Friedreich ataxia defect causes what cellularly?

Answer 40

mitochondrial iron accumulation = oxidative damage

Question 41

Friedreich ataxia repeats normal range?

Answer 41

5-33

Question 42

Friedreich ataxia repeats expansion can be?

Answer 42

66-1700!

Question 43

Friedreich ataxia mutable range is?

Answer 43

34-65

Question 44

problems with pre-symptomatic genetic testing?

Answer 44

ethical as there is not really much treatment

Question 45

SCA results interpretations,

Answer 45

REVIEW!!