Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Neuro > Huntington's Disease > Flashcards

Huntington's Disease Flashcards

1
Q

Most of the eukaryotic genome is non-repetitive. TRUE or FALSE?

A

FALSE

Most of the eukaryotic genome is repetitive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the function of repetitive DNA?

A
  1. None
  2. Structural - genome folding map
  3. Speciation - leads to genetic variability and is one of the reasons species diverge
  4. Regulate expression - ncRNAs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are ncRNAs

A

functional RNA molecules that are transcribed from DNA but not translated into proteins. In general, ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the bands apparent of chromosomes during DNA staining?

A

Repetitive DNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the types of repetitive DNA?

A

Satellite repeats (long runs of adjacent repeats): tandem (within) or terminal (end of DNA), mini or micro

Transposable elements (dispersed throughout genome): Retrotransposons or transposons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How did repeat expansion diseases change Mendelain genetics?

A

The child can have a disease much more severe or completely different from the parent or the child can have the disease when the parent doesn’t (even though most are dominant)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Give examples of expansion repeats that can cause disease

A

Fragile X syndrome (CGG)
Spinobulbar muscular atrophy (CAG)
Myotonic dystrophy (CTG)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are some common features of repeat expansion diseases?

A

Selective neurodegeneration
Correlation of repeat length with onset & severity
Midlife onset
Anticipation
Most dominantly inherited (gain of function)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is anticipation?

A

When the disease gets worse in severity along generations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are CAG repeat expansions called?

A

polyglutamine diseases because CAG codes for glutamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How common is Huntington’s?

A

1/15,000 (relatively common rare disease)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the mutation causing HD?

A

CAG expansion on chromosome 4 with more than 36 repeats

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the relation of penetrance to number or repeats

A

<36: normal
36-39: reduced penetrance
40+: full penetrance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the usual number of repeats and time of onset?

A

42 repeats and 40s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does repeat length affect onset?

A

As repeat length increases so does onset.

However, there is high variability per repeat of onset due to different genes + environmental factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe HD inheritance

A

It is autosomal dominant and shows anticipation especially when the father is the carrier

17
Q

Why is anticipation more common when the father is affected?

A

bc sperm is made throughout life and thus there is a higher risk of expansion.

Also evolutionarility most repeats favour expansion

18
Q

What is the mechanism of expansion?

A
  1. As the DNA polymerase is making new DNA strand, a hairpin forms C-G (bc repeats have lots of C and G - bases that can bind to each other on the same strand)
  2. A helicase comes and unwinds this new DNA strand
  3. The polymerase behind it uses everything including the hairpin as a template
  4. Expansion occurs
19
Q

What are the 3 general features of HD?

A

Movement problems, cognition, and psychiatric

20
Q

Describe the motor aspects of HD

A

Chorea - jerky movements
Abnormal eye movements (slow saccades, broken pursuit)
Impaired voluntary movement
Postural reflexes (falls)
Dystonia (repeated muscle contractions)
Dysarthria (unclear articulation of speach)
Dysphagia

21
Q

Describe the cognitive problems of HD

A

Executive dysfunction (impulsivity, planning, judgement)
Apathy and loss of initiative
Concentration and attention

22
Q

What is the most debilitating aspect of HD?

A

Depression and cognitive problems

23
Q

Why is do the cognitive problems begin to appear in HD?

A

Due to problems with the frontal lobe

24
Q

Describe the psychiatric problems associated with HD

A

Depression (most functionally debilitating)
Anxiety and panic disorders
Irritability
Obsessions and compulsions

25
Q

What are some systematic features of HD?

A

Weight loss and muscle wasting
Circadian disruption
Heart failure
Immune system problems

26
Q

How does juvenile onset differ from adult onset?

A 
<20years old
>55 repeats
Akinetic-rigid
Minimal chorea
Seizures
27
Q

Where is the huntingtin protein found?

A

It is ubiquitously expressed but more so in the cytoplasm than the nucleus

28
Q

What are the functions of huntingtin?

A

It is fundementally important for foetal development

  1. Embryonic nervous system development
  2. Synaptogenesis
  3. Intracellular trafficking
  4. Transcriptional regulation
29
Q

How is the brain affected in HD?

A 
The striatum (medium spiny neurons) atrophies first
Then the cortex begins to atrophy
30
Q

How does HD lead to toxicity?

A
  1. Aggregation
  2. Impaired protein degradation
  3. N-terminal fragments (the bits made when the protein gets chopped up)
  4. Disruption of transcription
  5. RNA toxicity (long RNA gets coiled up and accumulates in nucleus after binding to splice-regulating proteins)
  6. Synaptic plasticity (synaptic deficit)
  7. Mitochondrial dysfunction
  8. Cell to cell transmission of aggregates
  9. Glial dysfunction
31
Q

How do you diagnose HD?

A

•Genetic test
– Not in presymptomatic < 18y

• Genetic counselling (international protocol)

  1. Initial visit
  2. Second visit and blood test
  3. Result
  4. Follow up

• Prenatal and preimplantation testing

32
Q

What percentage of HD patients are negative for HTT mutation?

A

1%

33
Q

Out of the patients negative for HTT mutation how many are actually diagnosed?

A

~5%

34
Q

How do we treat HD?

A

Movement:

  • chorea: tetrabenzine (not any more) and olanzapine
  • Physiotherapy
  • Speach and language therapy

Psychiatric:

  • Antidepressants: citalopram, mirtazapine
  • Antipsychotics: Olanzapine, quetiapine
35
Q

Why is tetrabenzine no longer used to treat chorea?

A

Because it causes depression

36
Q

What are possible future therapies and how have the trials gone?

A
  1. Excitotoxicity (NMDAR antagonist -remacemide) didn’t do much
  2. Antiapoptotics (caspase inhibitors) tried only in mice
  3. Autophagy upregulation (Rilmendine)
  4. Transplantation (transplanting basal ganglia, medium spiny neurons in indirect pathway)
  5. Transglutaminase inhibitor (cysteamine)
  6. Antioxidants (Coznzyme Q10, Creatine) didn’t show efficacy
  7. Genome editing (CRISPR)
  8. Gene ‘silencing’ (antisense oligonucleotides)
37
Q

Why did most of the interventions on HD not work?

A

Because most were treating a problem downstream of the cause

Neuro (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions