Introduction / Background

In this case study, based on a true story (Ainsworth 2003; BBC News 2003), a 52-year-old mother of three sons needs a kidney transplant. She and her sons get blood tests to determine if any of the sons are suitable donors. But a few days later, Karen receives a distressing phone call. The nurse informs her that based on the blood test results she cannot be the mother of two of her three sons.

Most students have heard about situations in which the paternity of a child is questioned. Therefore, the current case study, in which maternity is questioned, should be of interest to them. The case asks students to develop hypotheses to explain how Karen cannot be genetically related to two of her three sons. Through an interrupted, progressive disclosure format, students develop hypotheses, then reject or revise these and formulate new ones as additional data are revealed. At the conclusion of the case, students are asked to consider the moral, ethical, and legal implications of Karen’s condition.

This case was originally written to be used in an introductory biology course, but could be adapted for a course in genetics or reproductive physiology. Students should have prior knowledge of the scientific method (formulating testable hypotheses), genetics, inheritance, formation of pedigrees, and basic human reproduction.

Objectives

Upon completion of this case study, students should be able to:

• formulate testable hypotheses given preliminary data;
• suggest tests to evaluate current hypotheses;
• interpret data to evaluate and revise hypotheses;
• draw a pedigree, given genetic information;
• use a Punnett square to predict the likelihood of a genetic combination; and
• discuss the condition of the protagonist of the case study and describe its implications.

Classroom Management

This case was developed to be completed in two 50-minute class periods, but it could easily be done in one 90-minute period. With some modification, it is also possible teach this case in one 50-minute class period, as described below. For this case, it is helpful to have plenty of board space or flip charts for students to share their ideas with the rest of the class.

Part I—Haplotypes (25 minutes)

I have tried giving Part I to students on the day of the discussion, but it significantly increases the time needed to teach the case and it seems to negatively affect the number of creative hypotheses that are generated by student groups. Therefore, I suggest giving this section to students ahead of time and assigning them the task of reading it over and answering the four questions at the end on their own. You may even want to offer an incentive to the group that generates the most hypotheses, which you can collect at the beginning of class the day of the discussion.

The day of the case, I start out by placing students in groups of three or four to share their responses to the questions, especially questions 3 and 4 (this takes approximately 5 minutes). During this time, I walk around the room listening to the different ideas in the groups and try to draw out the quieter students and encourage them to share their ideas. I try to refrain from supporting or discrediting any hypotheses.

I then follow up the small-group discussions with a whole-class discussion of the basic facts in the case (5 minutes) in which I ask students the following questions: Who is this case about? What is Karen’s problem? Why were blood tests done? What were the test results?

Students have trouble with the concept of a haplotype and HLA genes. In my introductory classes, I try to emphasize to the students that this is not the main focus of the case and that they will not be expected to understand all of the concepts related to HLA genes and transplantation. This is a topic that other instructors may want to expand upon depending on the course.

I then jump into the list of questions in Part I. Questions 1 and 2 are straight-forward and serve as a review of basic genetic principles (the answers are contained in the password-protected Answer Key—see below). I spend more time on Question 3, the students’ hypotheses to explain the test results. As the students or groups present these, I write each one on the board. I invite other students to think about each hypothesis presented, but I try not to discount any ideas (no matter how far-fetched) and give them all the same weight (10 minutes).

I then go down through the list of hypotheses written on the board and ask the students what could be done to evaluate each hypothesis (Question 4). I write their ideas (usually consisting of more tests or the gathering of additional information) next to the hypotheses they correspond to (5 minutes).

Part II—Pedigree (15 minutes)

Students are handed Part II and asked to read the short paragraph and answer the questions with their group members. I usually allow 5 minutes for this. I then appoint some of the first groups done to draw their pedigrees and Punnett squares on the board. I follow this with a brief discussion of Questions 5 and 6 (this is a good review of basic genetics: pedigrees, Punnett squares, probability). This is also a good time to address any student misconceptions or deficiencies in basic genetics knowledge (5 minutes).

I then go back to the section of the board containing the hypotheses and ask students to give me their feedback on Question 7—which hypotheses are still likely given the new data and which are not (5 minutes)? I then cross out hypotheses when the class agrees that they should be eliminated. I also add any new hypotheses that the students may think of at this point.

Part III—Family Members (10 minutes)

Students are given Part III of the case and asked to read the short paragraph and answer the questions that follow with their group members. After 5 minutes, I ask members of some groups (different ones this time) to add the new data to the existing pedigree on the board. I follow this with a short discussion of their additions to the board (2 minutes). Some groups may not have had time to answer Question 10, but I like to discuss this question as a class by crossing out hypotheses that are no longer valid (3 minutes).

Most students (depending on whether they have had exposure to this topic previously) will have exhausted all their possible hypotheses and only have a vague idea of what is happening but no way to explain it. It is very important in this step to assure students that they are not expected to know the answer. My students in the past have become frustrated at this point because we have eliminated all their hypotheses. If you are using this in a 50-minute period, you can stop at this point and continue with Part IV on the following class period.

Part IV—Hair and Thyroid (10 minutes)

Students are handed Part IV and asked to evaluate Figure 2 with their group members (5 minutes). I then discuss the data as a class, projecting Figure 2 on an overhead (5 minutes). Some students may have heard of this condition before; I ask them to explain their ideas thoroughly and ask other students for comment.

The test results in Figure 2 are taken from Yu et al., 2002, which outlines the analysis (PCR and sequence-specific oligonucleotide-probe hybridization) that was performed on Karen to determine her haplotypes. Figure 2 is not an immunoblot, but shows the results of an HLA Quick-Type kit from Lifecodes (see references in Answer Key).

This method uses polymerase chain reaction and sequence-specific primers to amplify the segments of DNA containing the HLA genes in such a way that single-stranded DNA is produced (uses unequal amounts of forward and reverse primers). Probes on microspheres are then added that are complementary to this single-stranded DNA. If a certain HLA allele is present in the DNA and was amplified during PCR, the probe will bind to the single-stranded DNA. These probes become fluorescent when hybridized to complementary DNA and this property is used for the detection of certain alleles in the DNA of interest. Figure 2 displays these results.

Part V—Conclusion (30–40 minutes)

Students are handed Part V and asked to read the text and evaluate Figure 3. This section gives an explanation of Karen’s condition and how the test results can be explained. I run this as a class discussion, making sure all students understand Karen’s condition and how it explains the test results.

I use the remaining time to examine some of the philosophical, moral, ethical, and legal implications of Karen’s situation and ask the students how they would feel if they were found to have this condition. I leave the remainder of the class period for this type of discussion, using such leading questions as:

• How would you feel if you found out you had this condition?
• What is Karen’s genetic and familial relationship to her sons?
• What medical implications does this have for Karen?
• Does the existence of people such as Karen have any legal implications (e.g., paternity tests, criminal investigations)?
• Instead of two female twins converging, what if it had been a male and a female (see Strain et al. 1998)?
• What are some moral and ethical implications for this case?
• What do you think scientists should investigate about people with this condition?

Depending on how talkative your students are, you may or may not have trouble filling the entire 40 minutes with this discussion. You may want to have information from other resources (such as those listed in References in the Answer Key) ready to present to the students on topics related to this case. Related topics such as polyploidy and mechanisms that prevent polyspermy may also be brought up for discussion if students have the appropriate level of background knowledge (see Kenyon College website and Heiter and Griffiths paper in the References section of the Answer Key). You may also assign a follow-up activity that the students can begin working on in class.

Answer Key

Answers to the questions posed in the case study are provided in a separate answer key to the case. Those answers are password-protected. To access the answers for this case, go to the key. You will be prompted for a username and password. If you have not yet registered with us, you can see whether you are eligible for an account by reviewing our password policy and then apply online or write to answerkey@sciencecases.org.

Follow-up / Extensions

The activities listed below may be used to supplement the case study:

• Students could be assigned to role-play by writing a letter from Karen to her sons explaining her condition and how she feels about it. This would give students practice describing what they have learned in their own terms and gaining perspective on a unique viewpoint. They could begin this letter in class if there is any leftover time.
• Students could be asked to write a response paper to the issues brought up in the case. They could comment on how they would feel if they were diagnosed with Karen’s condition.
• Students could be asked to write a paper on other aspects brought up in this case. Some possible paper topics could be: the various forms of this condition (twin, blood, whole body, mosaicism, etc.); other specific cases of this condition; the occurrence of the condition between mothers and children (exchange of cells during pregnancy); and the incidence of this condition with in vitro fertilization (IVF) technologies. Tell students to pretend they are a researcher and come up with questions that could be investigated related to this phenomenon. What studies could be conducted?
• For an upper-division course, students could be asked about the possible mechanisms for this condition (see Chen et al. 2005; Niu et al. 2002 in the References in the Answer Key). Did it occur through the fusion of two independent embryos or the fertilization of an ovum and its first polar body by two separate sperm?

Suggestions for Shortening the Case

To shorten the case for use in a single 50-minute class period, instructors can give Part I to students ahead of time. Collect the answers to Questions 1–4 at the start of class and then jump into a class discussion of the answers without allowing small group discussion first. Give Part V as a take-home reading assignment and assign students one of the follow-up assignments described above.

References

The references, which would reveal Karen’s condition, are not listed here, but in the password-protected Answer Key.

Acknowledgements: This case was published with support from the National Science Foundation under CCLI Award #0341279. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

Date Posted: 09/01/07

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