Ataxia Questions
How many CAG repeats are normal for an individual without CSA?
10
Which of the following is a normal amount of CAG repeats in healthy individuals?
10
How many CAG repeats are present in a normal, healthy individual?
10 repeats
At least how many molecules of glutamine must be present for the Purkinje cells to degenerate in spinocerebellar ataxia?
40
How many glutamines are necessary for a Purkinje cell to die?
40
Purkinje cells fire _____ times a second.
50
How many granule cells in the cerebellum?
70 billion
How many polyglutamine diseases exist today?
9
What explains the phenomenon where the DNA changes as it is passed from one generation to another and cause result in an earlier onset of disease.
A dynamic mutation
What explains anticipation?
A dynamic mutation to DNA that passes from one individual to another genetically
SCA 1 is said to be an anticipation disease meaning:
A genetic disorder is passed on to the next generation and the symptoms are seen earlier Anticipation is when a disease is passed down and symptoms are seen earlier in progenies)
Which of these neurons is significant in the coordination of movement?
A. Granule Cells B. Purkinje Cell C. Both A. and B. (CORRECT ANSWER)
Spinocerebellar Ataxia 1 is a progressive disease. While the first stage is balance difficulties, later stages include many symptoms listed below. Which is typically the ultimate cause of death?
A. Secondary infections B. Trouble swallowing C. Trouble breathing D. All of the above (CORRECT ANSWER)
What is the role of the Chaperone?
Added to misfolded shape proteins in order to get them back to a healthy shape
Spinocerebellar Ataxia1 (SCA1) follows what kind of inheritance pattern?
Autosomal Dominant
After researchers identified genes related to spinocerebellar ataxia, which method was primarily used to distinguish between the twenty two variations of SCA?
Blood Tests
Spinocerebellar Ataxia Type 1 is caused by the expansion of which trinucleotide repeat?
CAG
What trinucleotide repeat expansion causes SCA1?
CAG
Which gene mutation causes spinocerebellar ataxia?
CAG
The center of coordination, movement, and balance would be found wherein the brain?
Cerebellum
What part of the brain is referred to as the "little brain" and controls coordination and balance?
Cerebellum
What part of the brain is responsible for coordinating movement and balance?
Cerebellum
What part of the brain is the center of coordination of movement and balance?
Cerebellum
Where is the center for coordination and balance located within the brain?
Cerebellum
What is the name for the molecules that are added to a misfolded protein in order to return them to their normal function?
Chaperone
Which of the following is a protein that will "fix" a misfolded protein by changing its shape or taking it to the proteasome to be degraded?
Chaperone
How do Purkinje cells combat errors in protein folding?
Chaperones
Small helper proteins that can be refolded, denatured, or mutated proteins; the over-expression of these can suppress degeneration in certain diseases.
Chaperones
Spinocerebellar Ataxia (SCA1) is caused by dynamic mutations in Trinucleotide repeats. Which would you expect to see for a patient diagnosed with SCA1 in their 30s-40s?
D. 50 repeats of CAG
How does Spinocerebellar Ataxia type I get worse over time?
DNA polymerase "slips" on the CAG unit and a hairpin is formed, and then on the next round of replication the hairpin gets replicated, and therefore the CAG unit grows
There are subtle differences in each of the 22 kinds of Spinocerebellar Ataxia, however, they all have one commonality. Which of the following describes that similarity?
Degeneration of Purkinje Cells
What happens in type one spinocerebellar ataxia (SCA1)?
Degeneration of Purkinje cells
What is the general cause of SCA?
Destruction of Purkinje cells in the cerebellum
The anticipation of SCA can be attributed to what?
Dynamic mutations and expansion of a trinucleotide
What causes type one spinocerebellar ataxia (SCA1)?
Expansion of unstable CAG repeat
Polyglutamine diseases are all caused by the same neurons.
False
What is the role of chaperones?
Find misfolded proteins and change them to their functional shape
What are the first cells to receive information in the Cerebellum?
Granule Cells
What cells in the cerebellum receive information from the periphery first?
Granule Cells
Which cells in the cerebellum are the first to receive information from the periphery?
Granule Cells
What are the first cells in the cerebellum to receive information from the periphery?
Granule cells
What type of neurons in the cerebellum are the first to receive input from the periphery and the largest population of neurons in the central nervous system
Granule neurons
What is ataxia?
Impaired balance and coordination
Which of the following statements is FALSE regarding spinocerebellar ataxia?
In a family with a history of SCA, each successive generation has later onset.
What genetic mutation causes Spinocerebellar Ataxia Type 1, and how does it affect the phenotype?
Increase in CAG repeats, change in function
The onset of Spinocerebellar Ataxia (SCA) has been observed in younger patients through consecutive generations. This phenomenon is called anticipation and is due to what dynamic mutation?
Increase in the amount of CAG repeats for each generation
What is ataxia?
Loss of balance and coordination
What is Ataxia?
Loss of balance/coordination
In the Dr. Huda Zoghbi video, a case study was observed about a Montgomery, Texas family with Spinocerebellar Ataxia Type 1 (SCA1). Which of the following statements about the family's disease is false?
Only males were affected by the disease.
What is Anticipation in terms of a Neurologic Disease?
Onset of the disease earlier and earlier through generations
Neuronal degeneration is a common characteristic among many neurological diseases such as Huntington's, DRPLA, SCA, and SBMA. These diseases are referred to as _______. HINT: what do CAG repeats encode for?
Polyglutamine diseases
What are the common symptoms of spinocerebellar ataxia?
Problems with movement and balance
What is the protein complex that breaks down proteins through proteolysis when the protein's function has been carried out? Also known as the housekeepers.
Proteasome The proteasome is the protein complex that breaks down proteins)
What was found to be a common feature of neurodegenerative diseases?
Protein accumulation
What is the purpose of chaperone proteins?
Provide a healthy environment for proteins to fold properly
In SCA1, what type of cells degenerate first?
Purkinge cells
The biggest powerhouse cell in the cerebellum with many elaborate dendrites, fast-acting sending information via other neurons to the cerebral cortex
Purkinje Cells
Degeneration of what cells are most likely to cause balance and coordination issues?
Purkinje cells
What are the most active cells in the human nervous system?
Purkinje cells
What large cells found in the cerebellum degenerate due to SCA I?
Purkinje cells
What type of cell is affected by Spinocerebellar Ataxia Type 1?
Purkinje cells
In SCA type 1, what are the first cells to degenerate?
Purkinje cells Purkinje cells degenerate first
What neuron sends information via another neuron back to the cerebral cortex?
Purkinje fibers
What is the most important/busiest type of neurons in the cerebellum?
Purkinje neurons
Damage to Purkinje cells connecting the cerebellum to the cortex would NOT cause issues in which of the following actions?
Reflexive movement
Which of the following is not a polyglutamine disease?
SRTL
What is the function of the Purkinje cell?
Send information back to cerebral cortex to coordinate movement
What does SCA stand for?
Spinocerebellar ataxia
__________ is a genetic disorder characterized by slowly progressive incoordination of gait and is often associated with poor coordination of hands, speech, and eye movements.
Spinocerebellar ataxia
What is the definition of Anticipation as seen in spinocerebellar ataxia?
The onset of the disease is becoming younger as the generations go on, but have the same disease course
How does the length of the CAG repeats impact the onset of spinocerebellar ataxia?
The shorter the repeats, the later the onset
If you encounter 4 people with balance disorder's which one will you be able to tell just by looking at them
You will not be able to tell the difference in the balance disorders just by looking
Cerebral ataxia in a clinical setting was showing anticipation, which means it affected:
Younger generations in each generation
What is the job of chaperones?
a. Help a protein's folding b. Escort a protein to the proteasome e. A &B (CORRECT ANSWER
What are the symptoms of Spinocerebellar ataxia Type 1 (SCA1)?
a. Poor hand-eye coordination b. Dysarthria (abnormal speech) c. Problems with coordination and balance d. Disordered breathing and swallowing The correct answer is all above
Balance requires _____ neurons working together, in order for coordination to be accomplished.
all
Spinocerebellar ataxia is caused by...
an expansion of a trinucleotide repeat of CAG
What type of inheritance pattern of affected people is shown for SCA type I?
autosomal dominant
How do you diagnosis SCA1
blood test
What is known as the "little brain" that is the center of coordination and movement?
cerebellum
What biologically explains anticipation?
dynamic mutation changing over generations
SCA1 is caused by
expansion of unstable CAG repeat
What is ataxia?
impaired coordination
Spinocerebellar Ataxia type I is a degenerative disease of the Purkinje cells which affects balance and coordination in the affected patient. This disease is can be passed on to future generations and is shown to progressively get _________ with the progression of time.
worse