1a. 6-mercaptopurine reacted differently in the two girls due to the difference in metabolism. Laura being an athlete has a higher rate of metabolism and integrated more of the Thiopurine into her DNA at a faster rate. There was a different response between the two girls because Laura is allergic, and that is the reason why she showed adverse symptoms compared to Beth, who is non-allergic. Most of her normal cells were completely attacked by the drug. For effective management of Leukemia, doctors must consider the difference in enzyme variation among individuals.
1b. DR. Ryder might carry out the test of determining the level of plasma of the TGN in their bodies. 6-mercaptopurine is converted to TGN, and identifying the plasma levels helps in terminating the activity of the Thiopurine 6-mercaptopurine enzyme that activates the drug. Another test that the doctor should carry out is by determining the levels of TGN in both girls by running a DNA panel in both. Not the same quantity of the drug was absorbed and integrated in both of the two girls.
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Part II – Enzyme Activity
2a. Low: 0
Medium: 1
High: 9
The actual and observed number of patients will be different. This is because of the small sample size, where 1% of people have a low enzyme activity in a sample size of 10. This is just an estimation that causes deviations between the actual and observed data.
2b. Individuals inherit copies of the gene for the enzyme from each parent, and the level of inheritance follows a dominant/recessive pattern. Therefore, according to the graph, the high enzyme activity in some individuals is a result of dominant inheritance from the parents, while the low level of enzyme activity is from a homozygous recessive gene. The inheritance among the Caucasian community is because of the co-dominance pattern that made them exhibit a medium enzyme activity.
2c.The low bar and high bar represent homozygous for low enzyme activity while the medium bar represents heterozygously.
2d. Over 90% of the given population from the graph has high levels of TPMT enzyme activity. There is normal enzyme activity among the given population because most of them are heterozygous. However, the minority group representing 2% has a low enzyme activity. When considering the patient's Laura and Beth, Laura has a low TPMT enzyme level, whereas Beth has a high or medium TPMT enzyme level.
2e. The actual graph showed much more detail because it shows extreme cases where the minority of the Caucasian population are among the high region. The simplified graph shows only a rough estimate that is not real but is based on assumptions; thus, there are no extreme groups of the population found in the high or low regions.
Part III – TPMT Enzyme Activity Levels
3a The individuals with low enzyme activity are not able to eliminate the pharmaceutical, which leads to drug toxicity, thus attacking the normal cells. The effects of the drug are prolonged in individuals with low enzyme activity that attacks the normal cells and causing adverse effects on a person.
3b.According to the graph, the level of enzyme activity increases as the TGN level also decreases, and vice versa. For example, from the graph, when the TPMT level of enzyme activity increases from 8 to 14 units, the TGN units reduce from 800 to 400 units. Hence the activity of the TPMT enzyme is the key determinant of the conversion of the 6-mercaptopurine to its active form TGN. The conversion will be slower; thus, an alternative drug must be used to avoid the toxicity level.
Part IV – Putting It All Together
4. From her research, Dr. Ryder hypothesized that patients such as Laura (who became very sick upon receiving the drug) have very high /low TPMT enzyme activity and, therefore, very high /low levels of TGN nucleotides at normal doses. They easily became sick from the effects of the drug and could even die. These patients are homozygous /heterozygous for the version of the gene encoding high / low enzyme activity. A better drug dose for these patients is 1/10 th the level of other patients.
Patients such as Beth with high /low TPMT enzyme activity had high/low levels of TGN nucleotides. These patients would do well with the drug, and in some cases, might even need a larger-than-normal dosage for the treatment to be most effective. These patients were either homozygous for the version of the gene encoding high /low enzyme activity or were heterozygous.
Based on the graph in Part II, about 10% of the Caucasian population is homozygous /heterozygous .
Part V – SNPs and TPMT
5a. Kevin has a low level of enzyme activity because he is homozygous for TPMT 3A. Therefore, he will have 800 units of the TGN that will correspond with the eight units of the TPMT enzyme in the graph which will elevate the level of the TGN units.
5b. Because of the low enzyme level of the patient, Dr. Ryder should give him a lower dose of the drug, such as a quarter of that given to patients with higher enzyme activity. If he is given a normal dose, then he may suffer from a high level of toxicity that will result in adverse side effects and even death.
5c.It is important to understand one's TPMT DNA sequence because it helps in knowing the level and amount of drug to administer to a patient so as to eliminate any adverse effects that may occur to a person due to the toxicity of the drug. TPMT DNA helps in knowing how to manage patients and reduce adverse effects, especially those suffering from chronic illnesses such as cancer.
References
Chowning, J. T. (2010). Pharmacogenetics: Using genetics to treat Disease. National Center for Case Study Teaching in Science Case Study Collection. http://sciencecases. Lib. Buffalo. edu/cs/collection/detail. asp .
