A marathon runner has been exercising for over an hour. Which molecule helps provide a reserve supply of oxygen to muscle fibers?

Instructions to Candidates: There are five questions available from which you need to answer two of these. Each question is comprised of an essay (80% of marks) and short-answer questions (20%). All questions will be in the box below. Then, you will have two answer boxes below that. Within each answer box, please specify which question you are answering, for example: ‘This is my answer to Question X…’

Question 1 Short-answer questions (20%) Below is an image from G-banding analysis of a sample from a leukaemia patient. Abnormalities have been indicated by arrows. a) Using ISCN nomenclature, what is the karyotype of this individual? (2 marks) Below is an image generated by fluorescence in situ hybridisation (FISH) for Patient A, who is a newborn child displaying low birth weight, microcephaly, poor lung function, and a weak cry. The probes map to the q arm of chr12 (green) and the p arm of chr18 (red). b) What genetic abnormality is present in Patient A, and what diagnosis would be made? (2 marks) Below is an image generated by fluorescence in situ hybridisation (FISH). The probes map to 22q11.2 (red) and a control probe mapping to 22q13.3 (green). c) What genetic abnormality is present in the individual? (2 marks) d) The affected region is approximately 3 mb in size. Explain why FISH was used rather than G-banding for this patient. (4 marks) — Essay – 80% Critically evaluate G-banding, fluorescence in situ hybridisation (FISH) and CGH arrays for the detection of cytogenetic abnormalities. For each technique, explain how specific disorders could be diagnosed. Question 2 Short-answer questions (20%) Below is the output from analysis of the dystrophin (DMD) gene in a patient sample by multiplex ligation-dependent probe amplification (MLPA). a) What genetic abnormality has been identified in the patient sample? (2 marks) b) Why do MLPA probes contain a ‘stuffer’ sequence? (2 marks) c) The patient has no family history of muscular dystrophy. A blood sample from the patient’s mother was analysed and did not reveal any abnormality within the DMD gene. Explain the origins of the disease in the patient. (3 marks) d) A sample from a second patient revealed no insertions or deletions by MPLA. Explain why a diagnosis of Duchenne muscular dystrophy could not be excluded, and how diagnostic testing would proceed. (3 marks) — Essay (80%) Explain the pathogenesis of the Duchenne and Becker muscular dystrophies. In your answer, critically evaluate exon skipping as a novel therapeutic approach for treating patients. Question 3 A 65-year-old patient presents with weight loss, persistent cough and haemoptysis. A tumour biopsy is obtained and the KRAS gene is analysed by sequencing. The sequencing chromatogram is shown below. a) What type of DNA sequencing method was used to generate this chromatogram? (1 mark) b) Identify the nucleotide change present in the sample. (1 mark) c) Explain why two peaks are present at the mutation site. (2 marks) d) Is the mutation likely to be homozygous or heterozygous? Explain your reasoning. (2 marks) e) The highlighted codon is GGT. Using the chromatogram, determine the mutant codon and predict the amino acid substitution. (2 marks) f) Explain how this mutation may contribute to cancer development. (2 marks) — Essay (80%) Critically evaluate the use of genomic technologies for the diagnosis, prognosis and treatment selection of cancer patients. In your answer compare Sanger sequencing, targeted NGS panels, whole exome sequencing and liquid biopsy approaches. Question 4 Short-answer questions (20%) Below are the results of a genome-wide association study (GWAS) investigating genetic variants that affect levels of inflammation observed in patients with cardiovascular disease. a) Which SNP displays the strongest association with the phenotype? (2 marks) b) Why does the P value need to be so low and briefly explain your reasoning? (2 marks) The image below show a linkage disequilibrium for SNPs in a gene region: Which SNPs are in linkage disequilibrium? (2 marks) Explain briefly what a haploblock is? (4 marks) — Essay (80%) Critically evaluate the role of pharmacogenomics in personalised medicine incorporating examples from the lecture material. In your answer, explain how associations between single nucleotide polymorphisms (SNPs) and phenotypes can be identified through genome-wide association studies (GWAS). Question 5 Short-answer questions (20%) Below is a pedigree chart constructed to track a disorder within a family. a) What type of inheritance does the phenotype display? (2 marks) b) What is the probability that the proband will have an affected son? (2 marks) c) Explain why the proband may show symptoms of the disorder. (3 marks) Below is a pedigree for a different disorder, which is autosomal dominant: d) Using the pedigree, explain what is meant by the term non-penetrance. (3 marks) — Essay (80%) Incorporating examples from your lectures compare and contrast the pathogenesis of trinucleotide repeat disorders. Your answer should include at least three trinucleotide repeat disorders.

a). 

The action level is based on a 15-minute short-term exposure.

A Pathologists’ Assistant receives a routine gallbladder specimen. The specimen is opened, contents are noted, and a representative section is submitted. No gross abnormalities are identified. A single cassette is submitted for histology. Which CPT code most accurately corresponds to this specimen, and which component of the work is performed by the PA?

A Pathologists’ Assistant is part of a validation team assessing a new tissue processor. They run five identical samples and obtain nearly identical processing quality each time. This finding best supports which of the following validation outcomes?

A pediatric pathologist is reviewing two cases. Case A: Newborn with thin, lax abdominal skin, absent abdominal muscles, undescended testes, and renal dysplasia. Case B: Newborn with missing right pectoral muscle and webbed fingers on the right hand. Which of the following statements best distinguishes between the two cases?

Use the following narrative and data to answer questions 23– 27. A CEO is interested in comparing the effects of three different bottle designs (A, B, and C) on sales of a popular fabric softener. Fifteen supermarkets of equal sales potential are selected, and 5 of these supermarkets are randomly assigned to each bottle design. The number of bottles sold to customers in 24 hours at each supermarket is recorded. Assume all requirements for ANOVA are satisfied.                                          Bottles Sold   Design A Design B Design C Sample Size 5 5 5 Average 16.6 32.8 24.8 Variance 5.3 9.2 8.2 Std Dev 2.3 3.03 2.86     One-Way Anova Summary Source DF SS MS F-Stat P-value Between 656.13    

If the defect issue does not depend on the vendor, how many of the Made 4-U Co.’s parts would you expect to be perfect?