Download Examination: Molecular Medicine Course

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Examination: Molecular Medicine Course
Biomedicine Programme, term 5
Tuesday 15th January 2013
9am - 1pm
Please write your number on every page of your examination paper
This examination paper contains 8 questions and a total of 68 marks.
Answer all questions. Write on only one side of each page (do not
write on the back of a page).
Answers may be written in either Swedish or English, but we would appreciate the answers to
questions 5, 7 and 8 being written in English
A:
61 – 68 marks
B:
54.5– 60.5 marks
C:
47.5 – 54 marks
D:
41 – 47 marks
E:
34 – 40.5 marks
Fx:
32 – 33.5 marks
F:
< 32 marks
GOOD LUCK!
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Question 1
i)
A genome-wide association study (GWAS) can be performed with regard to either a
qualitative or a quantitative parameter. For example, a GWAS can be performed on a
group of patients with cardiovascular disease plus a group of matched control subjects
(a qualitative parameter), or the GWAS can be performed on a group of populationbased subjects in whom the plasma cholesterol concentration has been measured (a
quantitative parameter).
Many single nucleotide polymorphisms (SNPs) are analysed in a GWAS, but within
each of the two types of study, all the SNPs are analysed in the same way.
Explain, taking just one SNP as an example, how the results would be analysed in the
example of the cardiovascular disease patients + controls, and how the results would
be analysed with regard to cholesterol concentrations.
Specify clearly what comparisons are being made in each case and explain the
difference between the analyses performed in these two types of GWAS studies. (3p)
ii)
There are believed to be roughly 10 million SNPs in the human genome. The
companies that produce the SNP-arrays that are used in GWAS studies select only a
fraction of these SNPs to be included on the arrays. These SNPs are usually “tag
SNPs”. Explain what is meant by this and explain why it is desirable to use tag SNPs
in a GWAS. (3p)
iii)
After performing a GWAS, fine-mapping analysis is usually required. Explain what
fine mapping is and how it is performed and explain the purpose of performing such
an analysis. (3p)
iv)
A SNP that is strongly associated with disease is found to be located in the promoter
region of a previously uncharacterised gene. How would you investigate whether this
SNP has effects on transcriptional activity in vitro? Explain the experimental approach
you would choose and how the data from this experiment would be interpreted. State
clearly what comparisons you are making. (3p)
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Question 2
Answer ONE of the following questions (i.e. either A or B). (8p)
A) In an ELISA assay, one of the steps involves addition of horseradish peroxidaseconjugated streptavidin to the wells, after incubation with the secondary antibody.
i)
Outline the function of horseradish peroxidase and streptavidin and explain the
purpose of this step in the ELISA.
Controls are crucial for the interpretation of results and there are many different types.
ii)
Suggest one control that would allow you to determine whether the step described
above had been performed correctly.
iii)
Describe the results that would be expected from this control if the step described
above was performed correctly and if it was not performed correctly.
iv)
Suggest one other appropriate control for the entire ELISA assay and describe its
purpose/expected results.
B) During the extraction of RNA and DNA, water is added to the columns in one of the last
steps of the protocol prior to downstream analysis.
i)
Explain the purpose of this step and outline the function of the water and the columns.
ii)
Suggest one procedure that you could perform, which would allow you to determine
whether the step described above had been performed correctly.
iii)
Describe the results that would be expected from this procedure if the step described
above was performed correctly and if it was not performed correctly.
Controls are crucial for the interpretation of results and there are many different types.
iv)
Suggest one appropriate control for the TaqMan qPCR assay and describe its
purpose/expected results.
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Question 2
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Question 3
Atherosclerosis and its clinical consequences stroke and myocardial infarction are the leading
cause of death in the western world. A growing understanding of the atherosclerotic process
has led to some suggestions as to different treatment strategies. However, there are still many
unresolved questions regarding what strategy should be used.
i)
In order to be able to develop novel strategies to inhibit the atherosclerotic process, we
need detailed knowledge of the pathological process. Outline the key events leading to
the formation of fatty streaks. Make a schematic drawing to outline the different stages
of fatty streak formation. (3p)
ii)
In your opinion, which is(are) the optimal target(s) for drug treatment to inhibit fatty
streak formation? Explain your hypothesis. (2p)
iii)
In later stages of the disease, there are two major characteristics of a rupture prone
mature atherosclerotic plaque. What are they? Both are potential targets for drug
treatment to inhibit plaque rupture. Considering the underlying mechanisms, discuss
potential strategies for treatment. (3p)
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Question 3
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Question 4
i)
The principal function of adipose tissue is the regulation of fat storage and
mobilization. Which hormone is the key regulator in this context? Describe the steps
that this hormone regulates for both fat storage and mobilization in adipose tissue.
(3p)
ii)
Explain why it is so vital that fat storage and mobilization in adipose tissue is
appropriately regulated. Your answer should refer to the effects on other organs. (2p)
iii)
Discuss mechanisms that are believed to lead to the dysfunction of adipose tissue. In
your answer you should consider at least two different cell types within adipose tissue,
how their properties change when the tissue becomes dysfunctional, and the
consequences of these altered properties. (3p)
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Question 4
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Question 5
i)
Describe two independent pathways that elicit glucose uptake in healthy skeletal
muscle. For each pathway, please describe the external signal/hormone and the
signalling cascade leading to glucose uptake. How does type 2 diabetes impact upon
each pathway? (4p)
ii)
Skeletal muscle is an important organ for glucose uptake and storage. Describe how
glucose availability/uptake differs after lunch (post prandial) and after complete
digestion (post absorption) in healthy muscle vs diabetic muscle. Mention relevant
hormones, respiratory quotient and metabolic flexibility in your answer. (4p)
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Question 6
i)
Sarcoidosis is characterised at the histological level by a typical feature in the lungs.
Identify and describe this histological feature, explain which cells are important for its
generation, and speculate as to why such a feature is created. (3p)
ii)
The same (or highly similar) feature is also found in diseases other than sarcoidosis.
Name two such diseases. (1p)
iii)
Explain how the cells that accumulate in the lungs of patients with sarcoidosis are
made use of clinically when making a diagnosis. In your answer identify the cells
involved (there may be overlap with your answer to part (i)), describe the
methodology employed to characterise/quantify them, and discuss the properties and
functions of the cells. (4p)
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Question 6
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Question 7
i)
Tumours in the thyroid gland can often cause hyperthyroidism. List four symptoms
that may be present in hyperthyroidism. (2p)
ii)
Describe the differences between primary and secondary hypothyroidism, and their
consequences for the HPT (hypothalamic-pituitary-thyroid) axis. (3p)
iii)
A patient has a condition whereby the thyroid hormone transporter in the pituitary
gland is not functioning properly. What would be the physiological outcomes of this
defect? Explain why these outcomes occur. (3p)
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Question 8
i)
The pancreas can be said to have a “double role”. Explain what is meant by this and
discuss the morphology of the pancreas in relation to its different functions. Consider
the various cell types involved, their organization and function. (4p)
ii)
Pancreatic juice contains a number of components with distinct functions. Discuss the
roles of the following:
a) HCO3b) Pancreatic amylase
c) Chymotrypsin
d) Trypsin inhibitor
(4p)
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