NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

CASE TEACHING NOTES

for
“More than Meets the Eye: The Genetics of Eye Color”
by
Annie Prud’homme-Généreux, Life Sciences, Quest University, Canada

INTRODUCTION / BACKGROUND Objectives

The classic example of a human trait that behaves in a Through this case study, students will practice the
clear Mendelian fashion is human eye color. The gene following skills:
that controls it exists in two forms: a dominant brown • Link Mendelian genetics and phenotype with the
allele and a recessive blue allele. Students often wonder underlying molecular biology.
how green or hazel eyes are formed. Students asking • Explain the molecular basis of different eye colors.
this question have correctly identified that the genetics • Create and interpret Punnett squares for a single
of eye color is more complex than typically assumed. gene trait.
Furthermore, there are reports of cases that defy the • Create and interpret Punnett squares for two
expectations of a single gene trait: blue-eyed couples can unlinked genes.
give rise to a brown-eyed offspring. • Explain the appearance of novel phenotypes in
This case explores the molecular basis of eye color offspring that are not present in the parents.
using the story of a blue-eyed couple with a brown-eyed • Describe how biochemical pathways and genetic
child to explore the possible scenarios that could result complementation can explain the appearance in
in this outcome. The emphasis throughout the case is on offspring of novel phenotypes not present in the
linking Mendelian genetic concepts with the underlying parents.
molecular biology that can explain the resulting • Describe ways in which epigenetics can create
phenotype. With guidance, students will propose phenotypes in children not present in the parents.
several hypotheses that could account for the “blue × • Evaluate the likelihood of hypotheses based on
blue = brown” observations and weigh the likelihood of evidence and real-world information.
each of them against the evidence. The case ends with
a discussion of the evolution of human eye color and CLASSROOM MANAGEMENT
the implications of the ever-growing knowledge of the This case was developed for a 90-minute class. Students
genetics of eye color on our society. arrive to class having read a chapter in their genetics
The case was designed for second- or third-year biology textbook that provides an overview on regulation of
majors with a background in molecular biology and gene expression in eukaryotes. When they get to class,
genetics. Students attempting this case should have some there is a brief quiz to ensure that each student has taken
understanding of Mendelian genetics and the regulation responsibility for his or her learning. Students then break
of gene expression in eukaryotes. An introduction to into groups of three to five students. I distribute the printed
epigenetics would be beneficial, but can be incorporated materials for the first section of the case and give students
into this case (see discussion of Part IV below). The a pre-set amount of time for reading and group discussion
case may serve as an introduction to the concept of (the time allotted for each section varies - see below for
biochemical pathways and genetic complementation. details). This is followed by class discussion to combine
In the case, information is progressively disclosed to input and ensure everyone is on the right track. We then
students working in teams of three to five students. The proceed with the next section, reiterating these steps.
case takes approximately 1.5 hours to complete. Several For the class discussions, it is helpful to have access to
possible follow-up assignments are suggested below. an overhead projector or white or black boards with pens.

Case Teaching Notes for “More than Meets the Eye” by Annie Prud’homme-Généreux Page 1
 NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

Some instructors may have concerns about teaching I typically give students about 15 minutes to read Part
subjects that can have personal ramifications (i.e., I and brainstorm potential answers to the questions with
students doubting their parentage). In addressing this their team. I then use whole-class discussion to collate the
potential issue, I would like to point out the following: results of each team’s answers (particularly for Questions
High school biology typically uses the example of human 1 and 7), and to correct inaccurate information.
eye color to illustrate genetic transmission of a trait in
humans. It is a well known example. However, the way Part II – Eye Coloration (15 min)
it is presented in high school texts and classrooms is an This section of the case provides an overview of the
oversimplification since, in fact, it is possible for blue- molecular mechanism underlying eye coloration.
eyed parents to produce a brown-eyed child. Teaching Students are asked to reconsider their answers to
this case can actually serve to reassure some students who Question 1 in Part I in light of this information. Most
may have had questions about their parentage based on of the questions in this section ask students to reconcile
what they learned in high school. their knowledge of the genetics of eye color with the
molecular mechanism by which eye color arises. Students
Part I – High School Blues (15 min) first consider the possibility that more than a single gene
Part I introduces the problem: A couple with blue eyes is involved in the production of this trait. They then use
has a child with brown eyes. Armed with high school the information provided in this section to propose a
concepts of the genetics of eye color, the couple is genetic system by which three eye colors are possibly
puzzled. For the remainder of this case, students will produced. Finally, students are asked whether this added
attempt to determine whether a couple with blue eyes level of complexity can explain the “blue × blue = brown”
can have a child with brown eyes. situation that started this case.
Students are asked to review, share, and examine One aspect of this section that I would encourage
their knowledge of the genetics of eye color. In my teachers to clarify is the fact that melanin is not a protein:
experience, all students have had some exposure to the it is a chemical produced from tyrosine through a series
concept that eye color is a single gene trait and that the of chemical modifications. This is often a misconception,
brown allele is dominant over the blue allele. Students and this distinction needs to be clarified.
are asked to draw Punnett squares to confirm that,
according to common knowledge of human eye color Part III – Genetics of Eye Color (15 min)
genetics, the son does not appear to be a result of this In this section, students are provided with information
couple’s mating. Students are asked to consider what about the polygenic determination of eye color (the
cross could have resulted in this child’s genotype (i.e., to epistatic OCA2 and gey loci). Particularly, they are
determine the genotype of a biological father that could informed that eye color is determined by at least
account for these observations). two genes whose products interact to determine eye
The first question asks students about the molecular color. Armed with this information, students create
basis of eye color. While the genetics of eye color is often a Punnett square using two independently assorted
taught, most students have never considered what the genes to examine whether the brown-eyed son could be
eye color gene encodes, or how the brown and blue accounted for by this more complex genetic system of
gene product might differ in their function in the cell. determining eye color.
Among those students who have considered it, many While students understand the concept of unlinked
have assumed incorrectly that the eye color gene encodes genes, I find they often need help creating a Punnett
an eye color pigment. This myth will be dispelled later square for two unlinked genes. With the information
in the case when the molecular mechanism of eye color specific to this case, they often come up with the correct
production is explained. One of the goals of this case is result, but using incorrect methods that would not
to encourage students to link Mendelian genetics with work under a different situation (i.e., if the parents were
its underlying molecular basis to explain phenotype. heterozygotes for at least one of the genes). The key to
The last question in this part of the case encourages helping them with this exercise is to get them to list all
students to consider hypotheses to explain how a blue- the possible gametes that the mother and father can
eyed couple could have a brown-eyed child. create given their genotypes for the two genes. Once this

Case Teaching Notes for “More than Meets the Eye” by Annie Prud’homme-Généreux Page 2
 NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

is established, the rest of the Punnett square becomes Next, evidence is presented that students must
easy for students to complete. factor in to determine the likelihood of each of the three
The other challenge in this section (also related proposed hypotheses occurring. Students are then asked
to the Punnett square) is the concept that two genes to consider all the information that has been presented
(OCA2 and gey) interact to create one phenotype (eye in the case to evaluate whether Ryan is indeed Evan’s son,
color). Students will often report the phenotype as two and to indicate how certain they are of their conclusion.
phenotypes (one for each gene; for example, blue-blue), The questions lend themselves to a more open-ended
when in fact there is only one phenotype that is created discussion about the evolution of different eye colors
by the interaction of the two genes and therefore only and the implications of our growing understanding of
one should be reported. the genetics of eye color for our society.
Some students may feel uncomfortable with the
Part IV – What Else Could Be Going On? (20 min; more if open-endedness of this case. Which explanation is the
epigenetics needs to be explained) correct one? In this case, there is no definitive right answer.
The previous sections of the case have not given a Probability may direct us to favor one explanation over
satisfying explanation that could account for a creation another but several alternatives are possible. Further
of a brown-eyed child from two blue-eyed parents. testing would be necessary to reach conclusions. This
This section explores alternative molecular and genetic can be used as an opportunity to discuss with students
mechanisms that could account for this phenomenon. how science works by deductive reasoning.
Students are provided hints to three hypotheses and Alternatively, this case may be used to explore the
are asked to develop them. The first question should interaction of data and our explanation of it. Several of
point them in the direction of a reverse mutation, the the geneticists quoted in the case have offered hypotheses
second question makes them consider the possibility of about how blue-eyed parents could have brown-eyed
biochemical pathways and genetic complementation, offspring; however, while all of their explanations make
and the third question considers the influence of the sense, none of them may be correct. Yet even if none of
environment and possibly epigenetic mechanisms. the proposed explanations are correct, documented cases
Some information is provided in the questions to get of blue-eyed parents producing brown-eyed children
students thinking along the correct lines, but students would be proof enough that such an event can happen
must develop these ideas in more detail to understand whether or not geneticists can explain it.
the molecular basis of action.
If students do not have background information ANSWER KEY
on epigenetics, this would be a good time to provide it. Answers to the questions posed in the case study are
Epigenetics provides a molecular mechanism to link the provided in a separate answer key to the case. Those
effects of the environment on the genome. The University answers are password-protected. To access the answers
of Utah has created an interesting and interactive for this case, go to the key. You will be prompted for a
website to introduce this topic to undergraduate username and password. If you have not yet registered
students that could be useful (“Epigenetics,” 2010). This with us, you can see whether you are eligible for an
website includes teacher resources and lesson plans. It account by reviewing our password policy and then
will be important to apply the information learned apply online or write to answerkey@sciencecases.org.
about epigenetics back to the case. Having provided
an overview of epigenetics, ask students how this FOLLOW-UP / EXTENSIONS
mechanism could account for “blue × blue = brown.” Many follow-up activities and assignments may be used
to assess whether students learned the concepts explored
Part V – Three Hypotheses (20 min) in this case or to encourage students to research topics of
This section begins by presenting the three hypotheses interest connected to this case.
that could account for two blue-eyed parents producing • Prepare a concept map of all the ideas presented in
a brown-eyed child. Hopefully, students came up with this case that can explain how a blue-eyed couple
these hypotheses in the previous section, and this serves can have a brown-eyed child.
only as confirmation of their ideas. • Prepare a presentation of what the couple has
discovered about the eye color of their son and what

Case Teaching Notes for “More than Meets the Eye” by Annie Prud’homme-Généreux Page 3
 NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE

it reveals about the genetics of eye color. 18(1): 50-65. Retrieved 4 April 2010 from http://
• Write an opinion paper describing which www.jstor.org/stable/1535989
explanation of Ryan’s eye color the student favors, Kayser, M., Liu, F., Janssens, A.C., Rivadeneira, F., Lao,
backing up the position with data. O., van Duijn, K., et al. (2008). Three genome-wide
• Research what food or drug may affect eye color, association studies and a linkage analysis identify
and do a poster presentation of the findings. HERC2 as a human iris color gene. American
• Write a report on one of the three proposed Journal of Human Genetics 82(2):411-23.
mechanisms that may explain how “blue × blue = Nachman, M.W., and Crowell, S.L. (2000). Estimates
brown”: of the mutation rate per nucleotide in humans.
o Reverse mutations Genetics 156: 297-304.
o Genetic complementation “OCA2” (2009). Genetics Home Reference: Your
o Epigenetics Guide to Understanding Genetic Conditions. U.S.
• Prepare a brief paper that answers one of the National Library of Medicine. Retrieved 5 May
following questions: 2010 from http://ghr.nlm.nih.gov/gene=oca2.
o Some people assert that their eye color changes Starr, B. (2005). Ask a geneticist: Has any progress been
over time. Is there a biological basis for this made in explaining eye colors other than brown,
assertion? blue, and green? Understanding Genetics, The Tech
o What gives people grey eyes? Museum, Stanford University School of Medicine.
o Some people (and animals) have two eyes of Retrieved 2 April 2010 from http://www.thetech.
different color (e.g., a blue and a brown eye). org/genetics/ask.php?id=126.
Describe a few molecular mechanisms that Southworth, L. (2007). Ask a Geneticist: Are gray eyes
could account for this phenotype. the same as blue in terms of genetics? Understanding
Genetics. The Tech Museum, Stanford University
REFERENCES School of Medicine. Retrieved 2 April 2010 from
Belkin, D. (2006). Blue eyes are increasingly rare in http://www.thetech.org/genetics/ask.php?id=232.
America. The New York Times. Retrieved 2 April Sha, K. (2004). Ask a geneticist: How did I get green
2010 from http://www.nytimes.com/2006/10/18/ eyes? Understanding Genetics, The Tech Museum,
world/americas/18iht-web.1018eyes.3199975. Stanford University School of Medicine. Retrieved
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“Blue-eyed humans have a single common ancestor” ask.php?id=29.
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April 2010 from http://www.sciencedaily.com/ have a baby with brown eyes? Understanding
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Blue eye color in humans may be caused by a perfectly Starr, B. (2010). Ask a Geneticist: Why are blue eyes
associated founder mutation in a regulatory element so uncommon anymore?. Understanding Genetics,
located within the HERC2 gene inhibiting OCA2 The Tech Museum, Stanford University School of
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“Epigenetics” (2010). Learn. Genetics. Genetic Science thetech.org/genetics/ask.php?id=355.
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content/epigenetics/. Montgomery, G.W. (2008). A single SNP in an
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“The eyes have it on multiple gene question” (n.d.). The

University of Queensland Australia, Institute
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799-811.

Acknowledgements: This case was published with

additional 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 and do not necessarily
reflect the views of the National Science Foundation.

Copyright held by the National Center for Case

Study Teaching in Science, University at Buffalo, State
University of New York. Originally published January 13,
2011. Please see our usage guidelines, which outline our
policy concerning permissible reproduction of this work.

Case Teaching Notes for “More than Meets the Eye” by Annie Prud’homme-Généreux Page 5