Questions – Case Study on FFI - http://www-personal.umd.umich.edu/~jcthomas/JCTHOMAS/1997%20Case%20Studies/AAkroush.html
Further reading: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600072
1. Based on your research into Alzheimer’s disease and your interview, how are these two disorders alike?
-Answer- Alzheimer’s disease and fatal familial insomnia are similar because they both include degeneration of the neuron cells. Also both are due to protein misfolding; the alpha helix becomes beta sheets. Amyloid plaques build up in both diseases in the brain and the blocks neurotransmitter signaling. Amyloid deposits physically disrupt tissue architecture, suggesting disruption of function. Communication from the brain to the body and the body to the brain are not received due to this buildup. Both Alzheimer’s disease and fatal familial insomnia have the symptom of dementia. As for cures of the diseases, there are not any, but like Alzheimer’s Disease, they both look to use gene therapy in order to insert the correct gene into an affected individual altering his/her gene expression making it what it should be for the expression of the correct protein.
2. What are prions?
-Answer- Prions are mutated proteins that do not self replicate. Prions have been implicated in the formation of amyloid plaques that are seen in both FFI and Alzheimer’s. They are thought to infect normal proteins and change their folding structure. The altered structure is stable and resistant to denaturation which makes it difficult to dispose of them.
3. FFI is an autosomal dominant disease, meaning that if an individual inherits just one dominant allele from either parent, they will develop the disease. However, this disease does not manifest itself phenotypically until after reproductive age. So can this disorder be acted on by natural selection? What about Alzheimer’s? What is maintaining these disorders in the population?
-Answer- No this order cannot be acted on by Natural Selection because natural selection works on certain phenotypes, and even though the disease does not manifest phenotypically until after reproductive age, it is still present in the genotype. Therefore it can still spread without being selected against. By the time a person realizes they have the disease they will have probably reproduced and passed their genes to the next generation. Alzheimer's is the same way, since it only shows itself in the later stages of life, sufferers would have already spread their genes to the next generation before they realize they are carriers. These disorders remain in teh population because they only appear after the reproductive age, which is usually to late for them to be selected against.
4. FFI is caused by a single mutation that, in the presence of methionine at amino acid position 129, changes aspartic acid to asparagine. This same mutation, in the presence of valine at position 129, causes a separate prion-disease called Creutzfeldt-Jacob syndrome. In cattle, the homologous syndrome is Mad Cow disease. How can studying protein folding and mis-folding help in understanding diseases like these?
-Answer- Studying how this protein folds could possibly lead to future gene therapies by knowing how the properly folded protein looks and acts. This can allow for disease identification early in life and treatment options to help prevent a sad death and transmission to offspring. Since FFI is caused by protein mis-folding in the presence of a certain chemical, methionine, maybe the presence of another chemical could help change new proteins being made to fold correctly.
This disease was discussed last week on Medical Mysteries: (http://video.google.com/videoplay?docid=760959254431325673&q=fatal+familial+insomnia&total=3&start=0&num=10&so=0&type=search&plindex=0
5. The two sisters in this story lost their mother to FFI. One sister chose to be tested for the mutation, while the other sister did not. Would each of you want to know whether or not you had a disease such as this, or would you rather remain unaware?
-Answer-
- Kevin - I would want the test because I would then know how long I had to accomplish what I wanted in life and live it to the fullest.
- Victor - I would rather not be tested for it just because that if you know about it, you would be living in fear and that eventually you will die. There is not cure for it at the moment, so really there is no reason to know that you have it and if you were to have that genetic mutation you would worry that you will live a life of sickness and die. All in all, although knowledge is important in living, sometimes you have to say, “not this time” to understand to live your life to the fullest with no regrets.
- Megan - I would not get tested, because there’s no treatment for it; better to live my life without knowing that it will be cut short.
- Frank - I would want to be tested so that I am aware of whether or not I am going to suffer such a disease. At least that way I can get my priorities in life sorted before the disease hits me.
