Principles of Disease Investigation in Genetics and Genomics

FACULTY OF SCIENCE & ENGINEERING SCHOOL OF Biomedical Science and Physiology

ALTERNATIVE ASSESSMENT PAPER

Module Code         :         5BM044

Module Title           :         Principles of Disease Investigation in Genetics and Genomics

Date                        :         Sem 2 Resit July 2021

Examiners              :         Paraskevi Goggolidou, Iain Nicholl, Paul Kirkham, Katherine Karakoula, Mark Morris

INSTRUCTIONS TO CANDIDATES

        This is a paper with questions in accordance to the module’s learning

outcomes.

        You Should Attempt 4 out of 7 Questions, 2 from Section A and 2 from

Section B.

        Each answer needs to numbered correctly indicating relevant question.

        Read and follow ALL instructions

MATERIALS PERMITTED

        Reference materials, books, journals

Student Name & Number ………………………………………………………………….

Section A

Answer 2 questions from Section A.

All answers must be referenced (Harvard in-text citations together with completed reference list) and within the allocated word count.

500 word limit per question, supporting your findings with a minimum of 2 relevant references per question.

Question 1

a) Explain using diagrams, how the t(8;14)(q24;q32) karyotype arises, how it drives Burkitt Lymphoma (a B cell derived cancer) and how it is detected in a clinical laboratory setting. (15 marks)

b) Describe and critically evaluate the following variants seen in patients with suspected familial DNA mismatch repair defects. (10 marks)

GeneLocusNature
hMSH2c.289C>T(p.Gln97*)
hMLH1c.350C>T(p.Thr117Met)
hMLH1c.332C>T(p.Ala111Val)
hMSH6c.1519dupA(p.Arg507Lysfs*)

Question 2

a) Explain, using diagrams, how mutations in the APC gene can potentially arise; are detected in a clinical setting, and how such mutations can result in cancer formation in FAP. (15 marks)

b) Describe and critically evaluate the impact of the following genetic abnormalities on patients:

(1) 47, XXY (2) 45, X

(3) 45,X/47, XY+21

(4) 46, XX, del(5)(p15.3) seen in 38% of cultured cells

(10 marks)

Question 3

a) Explain in molecular terms how acetylation of histone lysine residues can impact on gene expression. (15 marks)

b) Cysteine is considered to be a polar amino acid and yet can be found inside the core of a protein. Explain why. (10 marks)

Question 4

a) IUPs & IDRs (intrinsically disordered proteins or regions) are identified by a unique property in their secondary structure that gives rise to their unfolded or disordered state. They can also be classified into two major functional groups. (i) What is this

property? and (ii) What are the two major functional classification groups, and the types of activity associated within in each group? (15 marks)

b) A protein purified by immunoprecipitation was found to give a single band of

80kDaltons molecular weight when analysed by non-reducing polyacrylamide gel electrophoresis (PAGE). In contrast when analysed by reducing PAGE it gave two bands of 15kDaltons and 50kDaltons. Finally when analysed by 2D gel electrophoresis using isoelectric focusing in the first dimension and a reducing PAGE in the second dimension, 3 distinct protein dots were observed. What does this tell you about the quartenary structure of this protein molecule? (10 marks)

Section B

Answer 2 questions from Section B.

All answers must be referenced (Harvard in-text citations together with completed reference list) and within the allocated word count.

500 word limit per question, supporting your findings with a minimum of 2 relevant references per question.

Question 5

a) With the use of diagrams, choose one of the central methodologies used to measure the transcriptome and explain its main principles from the starting point to the analysis of the results (15 marks).

b) Explain how the analysis of the transcriptome is used to improve understanding of disease mechanisms and to improve on disease diagnosis. Use an example to support your answer (10 marks).

Question 6

a) The relative concentration of proteins is the key determinant of cell morphology and function. Explain (using figures where appropriate) how epigenetic expression control by microRNAs contributes to variations in cellular protein levels. (15 marks)

b) During the development of Clear Cell Renal Cell Carcinoma (cRCC) there are many cellular pathways that are dysregulated via inappropriate promoter methylation of individual genes. Describe  how promoter  methylation  changes gene  expression. Using an example from cRCC consider how reduced expression of one protein may contribute to inappropriate cellular signalling (use figures where appropriate). (10 marks)

Question 7

a) Explain how BLAT works in bioinformatic analysis and show its value using two examples. (15 marks)

b) Compare and contrast BLAST and BLAT. (10 marks)