BIO2104 - A Diagnostic Assessment for Introductory Molecular and Cell Biology

Assignment Task

The problem solving (case studies) assessment will assess course learning outcomes 1, 2, 4 and 6. The total mark for this assessment is  marks and is worth 20% of your overall grade for this course. You must attempt and submit all assessment items in order to pass the course, including this assessment item.

Question

1. Please answer the following questions

a. What structure of the chromosome is stained in the karyotype below and what is the primary function of this structure?

b. What is the function of telomerase (please ensure that your response expands upon what is provided in Module 1)?

c. When chromosomes are broken by exposure to high-energy radiation (e.g. an X-ray), the resulting broken ends exhibit a pronounced tendency to stick to each other and fuse. Suggest why this might occur?

2. Mutations in the genes encoding α and β subunits of haemoglobin lead to haematological disorders such as a thalassaemia and sickle-cell anaemia. You found a family in China in which some members suffer from a new genetic form of anaemia. The DNA sequences at the 5’ end of the non-template strand of the normal and mutant DNA encoding the α subunit of haemoglobin are as follows:

a .State what type of mutation is present in the mutant haemoglobin gene? 

b. What are the codons in the translated portion of the mRNA transcribed from the normal and mutant genes?

c. What are the amino acid sequences of the normal and mutant polypeptides? 

d. Briefly describe the effect that the mutation above has on the final structure of the α subunit of haemoglobin. 

e. Please briefly outline how you determined your answer for the previous questions (i.e. please describe how you arrived at your answer for both part b and part c)? You must be able to complete this question to gain marks for questions part b and part c.

3. Please answer the following questions:

Look at the partially completed pedigree below, please state if the following progeny would be affected by the disease:

a. How did you determine who was and who was not affected by the disease in the pedigree above? You must be able to describe this in order to obtain marks for part a. 

b. Looking at the above pedigree demonstrating a disorder caused by mtDNA, what type of inheritance does mtDNA demonstrate and name one such disorder?

4. A 59-year-old woman presented clinically with the following:

• Weight-loss and night sweats
• Splenomegaly
• Pallor and dyspnoea
• Bruising
• Complaints of occasional blurry vision

The clinician ordered a full blood count and a general chemistry profile.

The following flagged results were returned:

From these results, the clinician requested a bone marrow biopsy for chromosomal analysis.

• State the most common type of treatment for this leukaemia type and briefly outline how this treatment works (i.e. what is its mechanism of action)
• Explain how this specific chromosomal alteration occurs. You may include a diagram here, but you must be sure to describe the diagram.
• Apply the correct cytogenetic nomenclature to this disease. 
• What abnormality/result would you expect cytogenetic analysis to show and what specific type of chromosomal alteration is this?
• Given the results indicated above, what type of leukaemia would you expect this patient to have? 

5. Look at the following karyotype of a young child, aged 5 months old:

• The diagram is highlighting a specific portion of a chromosome in this karyotype. Presuming that there was an abnormality in a gene detected at this chromosomal location, what autosomal disease would be indicated and what common, non molecular diagnostic assay would be used to determine the presence of this disease?
• What is the cellular basis for this condition? A diagram may assist your explanation. 
• Would any other testing be required for the child’s parents? Please justify your response. 

6. A mother took her 6-month-old baby to the family doctor. Her child was born with cleft palate. The mother of the child became worried about the child because the child always appeared to be sick, had laboured breathing and appeared to have developed cyanosis. She was also worried that her child hadn’t been able to roll-over and exhibited very little motor movement. She was also concerned that her child wasn’t as big as other babies that she had seen of the same age. Upon presentation, the doctor additionally noted a heart murmur, an underdeveloped chin and wide-set eyes with low set ears. The doctor also asked the child’s mother if the child had more trouble than usual with feeding, which the mother confirmed. The clinician ordered some blood tests, the results of which showed a slightly lowered lymphocyte count, thrombocytopaenia, hyperphosphataemia and hypocalcaemia. The clinician also referred the child to a paediatric cardiologist who requested a chromosomal analysis. The karyotype of this child is shown below:

• What would be your initial diagnosis based on the clinical evidence supplied above and what further cytogenetic testing would be required to confirm this diagnosis (if any)?
• What is the genetic basis of this disease and how/when is this thought to occur?
• Suggest a method for detecting this disorder prior to development of the first signs/symptoms and what type of sample would be used to ascertain this (if any). 

7. A 5-year-old male was taken to the family doctor. He was suffering what appeared to be recurrent respiratory infections. Even when he overcame these infections, he appeared to be having problems breathing. He was part of the local under six hockey team. However, over the last couple of months he had issues controlling his hockey stick and had suffered a few different injuries. Most of these injuries appeared to have been due to coordination issues or some kind of mishap. He exhibited syncope. He was also slow to get up from falling and this had transitioned to evenings where he struggled to get to his feet after lying down. He appeared to have a fluctuating gait as well, where he sometimes walked on his tippy toes. He had particularly well-developed calf muscles. His posture was unusual and demonstrated a slight curving of the spine. His pathology returned a raised serum creatine kinase (CK) result.

• What condition is this boy is suffering from and what is its inheritance pattern (i.e. sex-linked, autosomally inherited, recessive, dominant)?
• What is the gene involved in the development of this condition and where is it located within the human genome (i.e. what is its cytogenetic location)?
•  What is the cellular basis of this condition? 

8. Please answer all of the following:

• The following two separate karyotypes were reported for two different patients: 46,XY,del(8)(p11). 46,XY,dup(8)p11.
• Based on this information alone, which patient would be expected to be more severely affected by this mutation and why? 
• The following cytogenetic report reported the following karyotype and FISH result respectively:
• 46,XY,del(17)(p11.2). ish del(17)(p11.2p11.2)(D17S29-).

The FISH result is also demonstrated in the picture above.

What disorder do these results indicate (i.e. what is your diagnosis for this patient)?

• If the patient described in the above question (i.e. part b) reported a copy number variant of the same region and returned the following result provided below, then what would your diagnosis be? 

Result: ish dup(17)(p11.2p11.2)(D17S29++).

• Does the aCGH result shown below support your diagnosis for the condition listed in b) or c)? Please provide a short justification as to why the results validate your diagnosis as either the condition in b) or the condition in c) 

9. Please answer one of the following (i.e. a, b, or c):

• Is it possible to have an XX male? If so, how would this occur (be sure to include the molecular mechanism if this scenario is possible)?
• Is it possible to have an XY female? If so, how would this occur (be sure to include the molecular mechanism if this scenario is possible)? 
• It is possible to have an XYY karyotype. What are the primary characteristics/clinical features associated with this karyotype? What gene has been postulated to be the cause of these primary traits and briefly outline why? 

10. Acute lymphoblastic leukaemia (ALL) is not the only lymphoid neoplasm where hyperdiploidy results. Another relatively common lymphoid neoplasm exhibits hyperdiploidy in up to 90% of cases primarily with the gains of odd-unnumbered chromosomes, as shown by the results in the picture below. In this condition, the hyperdiploidy is usually seen without structural changes. Another common cause of this condition are aberrations resulting in trisomy 1q.

• What is the most likely lymphoid neoplasm described in the text above?
• Other than the cytogenetic findings, what other key laboratory results would you expect to see to confirm the diagnosis of this condition (keep this simple and only list the findings, e.g. elevated calcium. I do not expect you to outline why these are elevated or lowered)? 

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