Huntington's Disease Flashcards
Most of the eukaryotic genome is non-repetitive. TRUE or FALSE?
FALSE
Most of the eukaryotic genome is repetitive
What is the function of repetitive DNA?
- None
- Structural - genome folding map
- Speciation - leads to genetic variability and is one of the reasons species diverge
- Regulate expression - ncRNAs
What are ncRNAs
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.
What are the bands apparent of chromosomes during DNA staining?
Repetitive DNA
What are the types of repetitive DNA?
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 did repeat expansion diseases change Mendelain genetics?
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)
Give examples of expansion repeats that can cause disease
Fragile X syndrome (CGG)
Spinobulbar muscular atrophy (CAG)
Myotonic dystrophy (CTG)
What are some common features of repeat expansion diseases?
Selective neurodegeneration
Correlation of repeat length with onset & severity
Midlife onset
Anticipation
Most dominantly inherited (gain of function)
What is anticipation?
When the disease gets worse in severity along generations
What are CAG repeat expansions called?
polyglutamine diseases because CAG codes for glutamine
How common is Huntington’s?
1/15,000 (relatively common rare disease)
What is the mutation causing HD?
CAG expansion on chromosome 4 with more than 36 repeats
Describe the relation of penetrance to number or repeats
<36: normal
36-39: reduced penetrance
40+: full penetrance
What is the usual number of repeats and time of onset?
42 repeats and 40s
How does repeat length affect onset?
As repeat length increases so does onset.
However, there is high variability per repeat of onset due to different genes + environmental factors.
Describe HD inheritance
It is autosomal dominant and shows anticipation especially when the father is the carrier
Why is anticipation more common when the father is affected?
bc sperm is made throughout life and thus there is a higher risk of expansion.
Also evolutionarility most repeats favour expansion
What is the mechanism of expansion?
- 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)
- A helicase comes and unwinds this new DNA strand
- The polymerase behind it uses everything including the hairpin as a template
- Expansion occurs
What are the 3 general features of HD?
Movement problems, cognition, and psychiatric
Describe the motor aspects of HD
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
Describe the cognitive problems of HD
Executive dysfunction (impulsivity, planning, judgement)
Apathy and loss of initiative
Concentration and attention
What is the most debilitating aspect of HD?
Depression and cognitive problems
Why is do the cognitive problems begin to appear in HD?
Due to problems with the frontal lobe
Describe the psychiatric problems associated with HD
Depression (most functionally debilitating)
Anxiety and panic disorders
Irritability
Obsessions and compulsions
