Bio 363 Human Genetics Spring 2013
Atherosclerosis study sheet
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Lusis, 2000:
Make an outline or flow chart (as mentioned in the syllabus) of the events that lead to atherosclerosis, including examples of important gene products that contribute at each step. My own flow chart includes about ten steps. Don't get bogged down in all the details--try to flesh out what is important.

Oram, 2002
What is reverse cholesterol transport?
What happens to ApoA in people with Tangier disease?
Fig 1: What are the two models for how ABCA1 works? Which fits best with existing experimental evidence?
In what cell types in the body does ABCA1 function?
The text says that ABCA1 activity in macrophages is of minor importance to HDL levels-- what sort of experiment do you think was done to show this?
What's known about ABCA1 in biliary excretion? (What are bile salts?)
What is the function of ABCA1 in reverse transport? What experiments with knockout mice and transgenic mice overexpressing ABC1A were done to explore this? How is the experimental evidence conflicting?
How is the ABC1A gene activated? (What is a nuclear receptor?)
Is ABCA1 a good candidate for gene therapy for atherosclerosis? Are there other possible treatment approaches?

Pajukanta, 2004
What's the relationship between single-gene and complex forms of the same disease?
What's a SNP?
What are the three questions asked in the research paper to which this commentary refers?
Whose DNA was examined initially? How?
What was found? Then whose DNA was examined, and for what? How were common and rare variants treated differently in the experimental analysis?
What conclusions were made about the role of rare ABC1A variants in cholesterol levels in the population?
What were the conclusions about the role of common variants in cholesterol levels in the population?
What might have been missed?
Are there any implications for treatments?

Joyce et al., 2002
Which apolipoproteins (ApoA, ApoB, ApoE) are involved with the ABCA1 transporter, and which ones are associated with LDL and HDL?
There were two main comparisons in this study. What mouse genotypes were studied in each case? Why?
In the first comparison, what were the effects of the transgene on lipid and lipoprotein profiles? See the methods section for most abbreviations. For Fig. 1, note that CD stands for Regular Chow Diet and HFHC stands for High Fat High Cholesterol Diet.
How did the transgene affect atherosclerosis in the aorta?
What genotypes were compared in the second half of the paper? What was surprising? What might be the explanation for the unexpected results?
What do you think of the last two sentences of the paper--accurate or not? Should anything be clarified regarding this conclusion?