The goal of this assignment is to familiarize you with the process going from the characterization of a disease in human patients, to the identification of a mutated gene causing it, to the use of a mouse model to investigate how this mutation is causing the disease. You will learn about the spinocerebellar ataxia 1 (SCA1) genetic disease as an example of such a process.

This assignment is inspired by and uses content from, the lecture "A Healthy Nervous System: A Delicate Balance" on BioInteractive. Watch the following video, (it may also be useful to download the transcript for reference) and answer the questions below.

http://www.hhmi.org/biointeractive/healthy-nervous-system-delicate-balance

Question 1: Based on this video, describe the symptoms of the SCA1 disease.

Question 2: Explain how to read the chart by indicating what the squares and circles represent and what is the difference between filled and hollow shapes.

Question 3: Discuss what conclusions can be drawn from the pedigree eg assuming that the disease is caused by the mutation of one single gene, do you think this mutation is recessive or dominant? Are the affected individuals more likely to be heterozygous or homozygous for this mutation? Is the disease affecting equally men and women? For each conclusion, make sure to explain how it is supported by the pedigree.

Question 4: Based on the descriptions in OMIM and the information from the video, indicate what genetic mutation is responsible for the SCA1 disease and what consequence it has on protein primary structure.

Question 5: Which organ and cell type are primarily affected by the mutation? Is this consistent with the symptoms observed in SCA1 patients?

Question 6: From the video describe the phenotype of the SCA1 mouse. Is it similar to symptoms observed in SCA1 patients?

Question 7: Is SCA1 considered to be caused by a loss of function of the protein affected, or is it thought to be due to another mechanism?

Question 8: Based on the findings from the mouse model, researchers then developed an SCA1 model in Drosophila – what are the advantages of using a Drosophila model over a mouse one