Case Teaching Notes for
“Baby Doe v. The Prenatal Clinic: When Cell Division Goes Awry”

Introduction / Background

This case study is a “clicker case.” It combines the use of student personal response systems (clickers) with case teaching methods and formats. The case is presented in class using a series of PowerPoint slides in parts, or stages. After each stage, students are asked to respond to questions (called “clicker questions”) posed by the instructor. In this way, students work their way through the material to understand the problem presented in the case. Specifically designed for use in large introductory science classes, the method integrates lecture material, case scenario material, student discussion, (clicker) questions, clarification of the answers to those questions, more lecture, and data.

This case is designed for use in a large (>100 students) introductory biology course for either science or non-science majors. It presents a hypothetical court case in which a couple with a newborn baby with Down syndrome sues a small town clinic for malpractice. Students serve as expert witnesses in the case to explain to the jury what Down syndrome is, what could have happened to cause this syndrome in the baby, and whether the clinic could be found at fault. This requires that students understand the process of cell division and how the chromosomes behave during division.

Prerequisite Knowledge

Students are expected to be familiar with basic cell structure. A basic understanding of what DNA is and what it does as well as of the steps of cell division would be helpful, but is not necessary.

Objectives

After this case, students will be able to:

• Understand that DNA is stored on multiple chromosomes and that, during cell division, DNA is tightly compacted/packaged.
• Explain that cells/organisms may have multiple, slightly different versions of the same chromosome referred to as homologous chromosomes. Cells that contain one copy of each chromosome are said to be haploid. Cells that contain two copies are diploid.
• Describe what sister chromatids are and how they arise. DNA replication results in two identical copies of the same chromosome called sister chromatids. Sister chromatids remain physically connected together until near the end of cell division.
• Describe the major steps of mitosis/meiosis and what processes occur in each step.
• Draw a diagram and explain how the chromosomes behave during cell division and how this behavior differs between mitosis and meiosis.
• Explain how cells can have too many or too few copies of a chromosome due to errors during division and chromosome segregation.
• Understand that Down syndrome usually results from an extra copy of chromosome 21. (Partial copies can, though less frequently, result in the same syndrome.)
• Explain how other syndromes associated with errors in chromosome segregation such as Turner (XO), Kleinfelter (XXY), and XYY syndromes as well as aneuploidy in many cancers may have occurred.
• Describe how to use karyotypes to examine chromosomes in developing embryos.

Classroom Management

Although designed for use in a large course of 100 students or more, this case could be used or adapted for smaller classes. The case assumes that students are familiar with basic cell structure and function. Clicker questions are inserted into the PowerPoint slides for students to apply their understanding of the material presented, to encourage discussion, and to help the instructor determine if students understand the concepts being covered. The case is taught over two 50-minute class periods.

Teaching the Case

Slide 1, Slide 2, Slide 3, and Slide 4: Students are introduced to the case and are asked to assume that they are going to represent the medical clinic.

Slide 5: Presents the first clicker question (CQ#1). All of the answers represent actual causes of birth defects; this question can uncover potential misunderstandings early on.

Slide 6: This slide answers CQ#1 and gives some background information on the syndrome. Most cases of Down syndrome are due to problems that occur in cell division during gamete formation. The exact nature of the problem will be revealed later in the case. In cases of mosaicism, an error in cell division occurs during early fetal development. In cases of translocation, non-homologous recombination results in a partial copy of chromosome 21 attached to another chromosome.

Slide 7: The image on this slide shows the DNA present in a single E. coli bacterium. A human cell would have approximately 1,000 times more DNA in its nucleus than a bacterium. Copying and distributing this DNA to two daughter cells without it getting tangled, etc., is a challenging task for the cell. If the alternate image of a bacteriophage is used, humans have up to 10,000 times as much DNA.

Slide 8: This is an overview of how DNA is packaged. DNA does not exist as uncoiled strands in a cell. Instead it is wrapped around proteins (primarily histones) in a precise manner to form a protein/DNA complex called chromatin. When cells undergo division, the chromatin becomes more densely packed after replication, giving rise to the familiar “X” that most people imagine chromosomes look like. When chromosomes are packed into this dense structure, it is easier to move them around and protect the DNA from damage or entanglement with other DNA strands. I usually ask students what they normally do with their belongings before moving to a new apartment. A few should answer “packing” because it makes moving things easier and helps them avoid losing or breaking things.

Slide 9: Discusses how many chromosomes are commonly found in organisms, particularly humans (i.e., diploid, etc.), as well as what homologous chromosomes are. A good analogy for chromosomes is to bring four textbooks to class: two copies of the same textbook (sister chromatids), two different editions of the same textbook (homologous chromosomes), and one textbook for a completely different subject (non-homologous chromosomes).

Slide 10: CQ#2 is designed as an open-ended question. However, if your clicker type will only accept multiple-choice answers, you can add answer options to the slide for students to choose from.

Slide 11: Returns to the case. In order to figure out what may have caused the child to have too many copies of chromosome 21, students need to determine how cells get the right number of chromosomes normally.

Slide 12: This slide is an overview of the major aspects that take place during cell division. This case examines how the chromosomes are separated into the two daughter cells.

Slide 13: An overview of the cell cycle. Most cells in the body spend the vast majority of their time in G1, even more than indicated in this figure. During this time, cells carry out their normal duties. If a cell is capable of dividing and receives a signal from neighboring cells that it should do so, it will enter the S phase and duplicate its DNA. Once the DNA has been successfully copied, the cell enters G2. During this time, the cell finishes up preparations for division before entering the M phase. Together G1, S, and G2 make up Interphase. The M phase, when a cell is actively dividing, accounts for only a small part of the cell cycle.

Slide 14: The top half of the slide shows a single unreplicated chromosome at different levels of magnification. It consists of one DNA double helix. The bottom half shows a single replicated chromosome. It consists of two identical double helices. A common misconception is that many students believe chromosomes look like an “X” most of the time. In reality, this structure only exists after the DNA has been replicated and when the chromosomes have condensed. As you teach this, ask your students if the two copies of the chromosome are homologous chromosomes or sister chromatids.

Slide 15: An overview of the steps of mitosis. Some texts include ProMetaphase between Prophase and Metaphase. This slide can be covered quickly or skipped as most texts cover cell division very well.

Slide 16: CQ#3 checks if students understand the steps of mitosis and the behavior of chromosomes, specifically sister chromatids, during mitosis. If the students struggle with this question, encourage them to diagram the process of mitosis for a cell with 1–2 pairs of chromosomes. Have them give the name and the different components (homologous chromosomes, sister chromatids) at each stage of the process.

Slide 17: Segues into sexual reproduction. Most people are genetically unique. Identical twins are an exception to this rule. Find and insert pictures of celebrity families to illustrate how offspring may look similar to each other and/or their parents but not identical. Good examples might be:

• Martin Sheen (father), Charlie Sheen and Emilio Estevez (sons)
• Lloyd Bridges (father), Beau and Jeff Bridges (sons)
• Goldie Hawn (mother) and Kate Hudson (daughter)
• Steve (father) and Liv (daughter) Tyler
• Kirk (father) and Michael (son) Douglas
• Donald (father) and Kiefer (son) Southerland
• The Baldwin family
• The Osmond family
• The Jackson family

Slide 18: An overview of key reproductive differences between asexual and sexual reproduction.

Slide 19 and Slide 20: These slides point out that sexual reproduction requires a different kind of cell division, since the organism needs to produce cells with half the normal number of chromosomes. In animals, this type of cell division, meiosis, only occurs in the gonads.

Slide 21, Slide 22, and Slide 23: These slides point out the key differences between mitosis and meiosis. This is a good time to also point out how the chromosomes line up differently during mitosis and meiosis. Slide 21 shows how mitosis produces diploid cells, and meiosis produces haploid cells. Slide 22 repeats Slide 21 graphically. Mitosis produces identical cells, and meiosis produces different cells. The cell pictured has two pairs of chromosomes (large and small) and the different homologues for each are indicated by different colors. Slide 23 shows how mitosis involves one cell division, and meiosis involves two divisions. During Meiosis I, the homologous chromosomes line up. During Meiosis II, the sister chromatids line up. Ask the students to describe how the original parent and daughter cells compare for both mitosis and meiosis.

Slide 24: This is not a clicker question, but is asked simply to promote discussion. Ask your students how many unique gametes a cell with two pairs of chromosomes could produce. Each pair of homologous chromosomes line up independently of the others during metaphase of Meiosis I—referred to as independent assortment. As a result, the chromosomes in this organism could line up in two different ways giving rise to four genetically different gametes. A good extension to confirm students’ understanding of this concept is to ask them how many possibilities would exist for a cell with three sets of chromosomes.

Slide 25: Humans have 23 pairs of chromosomes. As a result, independent assortment by itself enables over 8 million unique gametes to be produced. A couple could produce over 64 trillion unique offspring.

Slide 26: In addition to independent assortment, the exchange of equivalent portions of homologous chromosomes (crossing over) produces new variations of chromosomes. Crossover occurs randomly along the length of each chromosome. Thus, a single individual can produce far more than 8 million unique gametes.

Slide 27: CQ#4 checks if students understand and can recognize chromosome behavior during mitosis.

Slide 28: CQ#5 checks if students understand and can recognize chromosome behavior during meiosis.

Slide 29: It is possible to identify the different homologues for a chromosome in an individual; this is indicated in this slide by using different colors for the chromosomes. CQ#6 uses this concept to test if students understand the outcome of meiosis.

Slide 30: Returns to the case and reminds students that they need to apply what they have learned about cell division to defend their client.

Slide 31: CQ#7 asks students to apply their understanding of cell division to explain how a cell can get an extra copy of a chromosome. The other answers (except E) are actual problems associated with cell division but would not result in the incorrect number of chromosomes. Except for a small number of exceptions, such as red blood cells that eject their nucleus when they mature, virtually every cell in a person’s body has exactly the same chromosomes as every other cell. It is helpful to show an animation or video of non-disjunction to help students visualize what happens during this process. Some potential sources:

• http://www.ecu.edu/mts/stage/genetics.htm
• http://www.biostudio.com/a_sitemap.htm
• http://www.mtholyoke.edu/courses/rfink/Videopages/video8.htm
• http://www.youtube.com/watch?v=PzTwnmF6g54

Slide 32: This slide compares normal meiosis in a cell with two pairs of chromosomes and a cell in which non-disjunction has occurred during Meiosis II. The sister chromatids for the small red chromosome have not separated properly in one of the cells.

Slide 33: Describes the situation in the case showing the homologous copies of chromosome 21 in the two parents and the child. The child has three copies of chromosome 21.

Slide 34: CQ#8 asks the students to use their understanding of meiosis to explain how the child ended up with an extra copy of chromosome 21. A good student might ask if it is possible for non-disjunction to have occurred during mitosis in the infant. This is a possibility but is relatively rare; only 1–2% of Down syndrome cases are formed by this method. Also, the number of cells that would display trisomy 21 will depend on when during development non-disjunction occurred.

Slide 35: CQ#9 further checks if the students understand when/where the mistake occurred.

Slide 36 and Slide 37: These slides raise a further issue of how we know if the child has Down syndrome other than through symptoms after birth. A developing fetus is most commonly checked for Down syndrome through a karyotype. Cells are collected from the embryo and treated with a chemical to stop cell division. The chromosomes are stained and the cells are then “squashed” on a slide to spread out the chromosomes. The chromosomes in a cell are photographed and images of individual chromosomes are cut out and lined up. A normal karyotype would have two complete copies of each chromosome and no more.

Slide 38: CQ#10 checks if students can apply their understanding of the steps of cell division to the process of karyotyping.

Slide 39: CQ#11 asks students to interpret a karyotype and apply their understanding of chromosome number.

Slide 40: Provides information about the risks associated with karyotyping and the link between Down syndrome and maternal age. The age of the woman with the Down syndrome child in the case is shown in red.

Slide 41: CQ#12 asks students to make a judgment call as to whether the clinic should be held responsible for not having tested the possibility of Down syndrome during the woman’s pregnancy.

Slide 42: These are examples of actual lawsuits involving Down syndrome and pre-natal testing.

Slide 43: The new recommendations for Down syndrome testing as of 2007.

Questions for Further Discussion

• What are the different forms of Down syndrome? How are they similar and how are they different? How do they arise? Do some forms more severely affect the developing fetus than others? Is non-disjunction limited to meiosis? How might the fetus be affected if non-disjunction occurred during mitosis earlier or later in development?

• Why does an extra copy of a chromosome interfere with normal embryonic development? Why does Down syndrome affect so many different tissues and organs? What treatments are there for Down syndrome? What kind of life can a Down syndrome child expect today? Fifty or 100 years ago?

• Men and women differ in the number of X chromosomes present inside of their cells. Why don’t these differences in chromosome number lead to problems similar to Down syndrome?

• What other birth defects and syndromes can you name? What are their causes? Are there other diseases associated with non-disjunction?

• What other diseases can be found by pre-natal testing? What additional methods might these tests use? What are the pros and cons of pre-natal testing?

Assessment

This case was developed as part of an NSF-sponsored grant (# DUE 0618570) to determine whether clicker cases such as this one produced greater learning than the traditional lecture approach. As part of that project, the clicker cases had questions that were asked of students, typically both before and after the class in which the material was presented, and again on the final exam. The assessment questions developed for this case, and their answers, are presented in the Answer Key.

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.

References

Down syndrome Information

National Down syndrome Society: http://www.ndss.org/

National Association for Down syndrome: http://www.nads.org/

National Down syndrome Congress: http://www.ndsccenter.org/

Mayo Clinic Down syndrome information: http://www.mayoclinic.com/health/down-syndrome/DS00182

Recommendations for Down syndrome Testing

http://www.acog.org/from_home/publications/press_releases/nr01-02-07-1.cfm

Karyotyping

http://www.nature.com/scitable/topicpage/Karyotyping-for-Chromosomal-Abnormalities-298

Slide Credits

Unless specifically indicated otherwise below, all illustrations appearing in this case study were created by the author, Norris Armstrong.

Acknowledgements: This material is based upon work supported by the NSF under Grant No. DUE-0618570. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the NSF.

Date Posted: January 15, 2010.

Copyright © 1999–2010 by the National Center for Case Study Teaching in Science.  Please see our usage guidelines, which outline our policy concerning permissible reproduction of this work.