Human Genetic Variation
Human Genetic Variation
Human Genetic Variation
6 BOOK COLLECTIONS
BSCS Development Team Videodiscovery, Inc. Administrative Staff
Joseph D. McInerney, Co-Principal Investigator D. Joseph Clark, President
Lynda B. Micikas, Co-Project Director Shaun Taylor, Vice President for Product Development
April L. Gardner, Visiting Scholar
Diane Gionfriddo, Research Assistant National Institutes of Health
Joy L. Hainley, Research Assistant Bruce Fuchs, Office of Science Education (OSE)
Judy L. Rasmussen, Senior Executive Assistant Karina Boehm, National Human Genome Research
Barbara C. Resch, Editor Institute (NHGRI)
Janie Mefford Shaklee, Evaluator Vence Bonham, NHGRI
Lydia E. Walsh, Research Assistant Larry Brody, NHGRI
Anne Westbrook, Science Educator Lisa Brooks, NHGRI
Carla Easter, NIGRI
Videodiscovery, Inc. Development Team Barbara Fuller, NHGRI
D. Joseph Clark, Co-Principal Investigator Kathy Hudson, NHGRI
Shaun Taylor, Co-Project Director Cynthia Allen, OSE
Michael Bade, Multimedia Producer William Mowczko, OSE
Dave Christiansen, Animator Gloria Seelman, OSE
Greg Humes, Assistant Multimedia Producer Lisa Strauss, OSE
Lucy Flynn Zucotti, Photo Researcher David Vannier, OSE
iii
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Student Lessons
Lesson 1—Alike, But Not the Same . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63
Lesson 2—The Meaning of Genetic Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .71
Lesson 3—Molecular Medicine Comes of Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .87
Lesson 4—Are You Susceptible? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .97
Lesson 5—Making Decisions in the Face of Uncertainty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .107
Masters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
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Foreword
This curriculum supplement, from the NIH develop problem-solving strategies and critical-
Curriculum Supplement Series, brings cutting-edge thinking skills.
medical science and basic research discoveries
from the laboratories of the National Institutes Each of our curriculum supplements comes with a
of Health (NIH) into classrooms. As the largest complete set of materials for teachers, including
medical research institution in the United States, extensive background and resource information,
NIH plays a vital role in the health of all Americans detailed lesson plans, masters for student worksheets,
and seeks to foster interest in research, science, and a Web site with videos, interactive activities,
and medicine-related careers for future generations. updates, and corrections (as needed). The
NIH’s Office of Science Education is dedicated to supplements are distributed at no cost to educators
promoting scientific literacy and the knowledge and across the United States upon request. They may
skills we need to secure a healthy future for all. be copied for classroom use but may not be sold.
The curriculum supplements enable teachers I hope you find our series a valuable addition
to facilitate learning and stimulate student to your classroom and wish you a productive
interest by applying scientific concepts to school year.
real-life scenarios. Design elements include a
conceptual flow of lessons based on the BSCS Bruce A. Fuchs, Ph.D.
5E Instructional Model (page 3), cutting-edge Director
science content, and built-in assessment tools. Office of Science Education
Activities promote active and collaborative National Institutes of Health
learning and are inquiry-based to help students supplements@science.education.nih.gov
________________________
1
The National Academy of Sciences released the National Science Education Standards in 1996, outlining what all citizens should understand
about science by the time they graduate from high school. The Standards encourages teachers to select major science concepts or themes
that empower students to use information to solve problems rather than stressing memorization of unrelated information.
v
About the National Institutes of Health
Founded in 1887, NIH is the federal focal point and clinical investigators, as well as the myriad
for health research in the United States. Today, professionals in the many allied disciplines who
NIH is one of the agencies within the Department support the research enterprise. These efforts
of Health and Human Services. Its mission is also help educate people about scientific results
science in pursuit of fundamental knowledge so that they can make informed decisions about
about the nature and behavior of living systems their own—and the public’s—health.
and the application of that knowledge to extend
healthy life and reduce the burdens of illness This curriculum supplement is one such education
and disability. NIH works toward meeting the effort. It is a collaboration among the National
mission by providing leadership, direction, and Human Genome Research Institute, the NIH
grant support to programs designed to improve Office of Science Education, Biological Sciences
the health of the nation through research. Curriculum Study, and Videodiscovery, Inc.
NIH’s education programs contribute to ensuring For more about NIH, visit http://www.nih.gov.
the continued supply of well-trained basic research
vi
About the National Human Genome
Research Institute
The National Human Genome Research Institute should be able to determine his or her risk
(NHGRI) is leading the international effort to for disease through genetic tests. If the tests
identify and characterize the estimated 20,000 indicate increased susceptibility to a disease, the
to 25,000 genes that orchestrate a single cell’s individual will be able to obtain counseling on
development into a human infant and then into how to reduce that risk—perhaps by periodic
an adult, and that govern whether that individual medical check-ups, a special diet and other
will be susceptible to diseases such as muscular lifestyle changes, as well as drugs tailored to
dystrophy, cancer, Alzheimer disease, high blood his or her genetic profile. Treatment of disease
pressure, and obesity. will also likely include gene therapies to replace,
compensate for, or repair the genes that play a
Part of the National Institutes of Health, the role in the disease.
Federal government’s biomedical research arm,
NHGRI set the year 2005 as its deadline for In addition to genetics research, NHGRI sponsors
completing the DNA sequence of the human research exploring the potential ethical, legal,
genome, our genetic blueprint. On April 14 of and social consequences of the anticipated
2003, NHGRI, the Department of Energy, genetics revolution in medicine. By focusing now
and their partners around the world announced on preventing the potential misuses of genetic
the successful completion of the Human information in insurance and employment,
Genome Project. NHGRI is helping ensure that genetic information
will be used as it was intended: to promote
Completing the sequence of the human genome human health and save lives.
and deciphering its functions are the first step
toward “molecular medicine,” the revolutionary For more information about the National Human
approach to diagnosis and treatment that will Genome Research Institute, visit its Web site at
create targeted, individualized health care http://www.genome.gov.
in the early 21st century. Then, each person
vii
About Biological Sciences Curriculum Study
viii
Introduction to
Human Genetic Variation
This module has two central objectives. The the practice of medicine, and it is vital that citizens
first is to introduce students to major concepts recognize these changes and are prepared to deal
related to human genetic variation. Homo sapiens with them. Being prepared involves understanding
comprises a single species, yet the more than the basic science that underlies new medical
6.9 billion of us alive today, and the millions practices and therapies and recognizing the
who preceded us following the emergence of fully complex issues and questions that some of these
modern humans some 150,000 years ago, are a procedures and therapies raise. Thus, students
diverse lot. One look at the students who sit in will have the chance to think about how the
your class each day is all you need to confirm detailed analysis of human genetic variation
that fact. The module’s first objective is to help is already changing their lives.
students recognize and understand this variation.
If recognizing human variation is common, it is
The second objective is to convey to students the not new; certainly our ancestors realized that no
relationship between basic biomedical research two humans are identical. Nevertheless, biologists
and the improvement of personal and public before Charles Darwin subscribed to what Ernst
health. The knowledge that scientists gained as Mayr called essentialist thinking: the notion that
they sequenced the human genome is changing each species is defined by an invariant type that
limits the ability of its members to vary too much
from the essential nature of the species. Among
Darwin’s great insights was the recognition that
the essentialist view is incorrect—the members of
any given species are actually highly variable—
and that some variations within a species will confer
selective advantage on those individuals that possess
them. This variation within species makes
differential selection, and therefore evolution,
possible. Mayr called this view population
thinking, and it pervades modern biology.
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Human Genetic Variation
The identification of DNA as the genetic material • Studying the genetic and environmental factors
in the early 1940s and the elucidation of its involved in multifactorial diseases will lead to
structure about a decade later opened the way for improved diagnosis, prevention, and treatment
an analysis of genetic variation at the molecular of disease.
level. That analysis proceeds at breakneck speed • Our growing understanding of human genetic
today, propelled by a host of powerful new variation will allow us to identify genes
techniques in molecular biology. associated with common diseases such as
cancer. Genetic testing to identify individuals
This module focuses on our progress in analyzing who have variations that make them
human genetic variation and the impact of that susceptible to certain diseases can help people
analysis on individuals and society. There are many make decisions in uncertain circumstances and
concepts we could have addressed, but we have holds the prospect for more effective prevention
chosen, with the help of a variety of experts in and treatment. However, this capability also
this field, a relatively small number for exploration raises difficult questions about the uses of
by your students. Those concepts follow. genetic information—questions that illustrate
• Humans share many basic characteristics, but the personal and social implications of
there is a wide range of variation in human biological research.
traits. Most human traits are multifactorial:
They are influenced by multiple genes and We hope the module’s five lessons will be effective
environmental factors. vehicles for carrying these concepts to your
• The ultimate source of genetic variation students. Although the activities contain much
is differences in DNA sequences. Most of interesting information about various aspects of
those genetic differences do not affect how human genetics, we suggest that you focus your
individuals function. Some genetic variation, students’ attention on the major concepts the
however, is associated with disease, and some module was designed to convey. The concluding
improves the ability of the species to survive steps in each lesson are intended to focus the
changes in the environment. Genetic variation, students’ attention on those concepts as the lesson
therefore, is the basis for evolution by natural draws to a close.
selection.
• One of the benefits of understanding human
genetic variation at a molecular level is its
practical value for helping us understand and
treat disease. The development of effective
gene-based therapies is an exciting outcome
of human genetic research. These therapies,
however, are potentially many years away for
many diseases.
2
Implementing the Module
The five lessons in this module are designed to be • to experience the process of inquiry and
taught either in sequence, as a supplement to your develop an enhanced understanding of the
standard curriculum, or as individual activities nature and methods of science, and
that support or enhance your treatment of specific • to recognize the role of science in society
concepts in biology. The following pages offer and the relationship between basic science
general suggestions about using these materials in and personal and public health.
the classroom; you will find specific suggestions
in the support material provided for each lesson. What Are the Science Concepts and
How Are They Organized?
What Are the Goals of the Module? We have organized the activities to form a conceptual
Human Genetic Variation is designed to help whole that moves students from an introduction
students reach the following major goals to human genetic variation (Alike, But Not the Same),
associated with biological literacy: to an investigation of its biological significance
• to understand a set of basic scientific principles (The Meaning of Genetic Variation), to a discussion
related to human genetic variation, of some of the practical implications of human
3
Human Genetic Variation
genetic variation for the treatment of disease Despite their current popularity, many teachers
(Molecular Medicine Comes of Age and Are You think of active, collaborative, and inquiry-based
Susceptible?), and, finally, to a consideration of learning rather generically. Defining these three
how understanding human genetic variation key terms specifically will provide a foundation
can affect the decisions we make about our on which we can build a detailed description of
own health (Making Decisions in the Face of the instructional approach that the five lessons
Uncertainty). Table 1 summarizes the sequence in this module advocate and implement.
of major concepts addressed by the five lessons.
Conceptually the broadest of the three, active
Although we encourage you to use the lessons learning means that students are involved in
in the sequence outlined in Table 1, many of “doing things and thinking about the things
the lessons can be taught individually, to they are doing” (Bonwell and Eison, 1991, p. 2).
replace or enhance a more traditional approach These authors elaborate by listing the following
to the same or related content. Table 2 provides characteristics typically associated with strategies
recommendations for inserting the lessons into that deserve to be labeled “active”:
a standard high school curriculum in biology. • Students are involved in more than listening.
• Instructors place less emphasis on transmitting
How Does the Module Correlate information and more emphasis on developing
with the National Science students’ skills.
Education Standards? • Students are involved in higher-order thinking
Human Genetic Variation supports teachers in (for example, analysis, synthesis, and
their efforts to reform science education in the evaluation).
spirit of the National Research Council’s 1996 • Students are engaged in activities (for example,
National Science Education Standards (NSES). reading, discussing, and writing).
Table 3 lists the content and teaching standards • Instructors encourage students’ exploration of
that this module primarily addresses. their own understandings, attitudes, and values.
How Does the BSCS 5E Instructional Most teachers endorse the use of active learning.
Model Promote Active, Collaborative, We know intuitively, if not experientially and
Inquiry-Based Learning? explicitly, that learning does not occur through
The activities in this module are designed to passive absorption. But often, we do not realize
offer students the opportunity to participate in how active students must be for real learning to
active, collaborative, and inquiry-based learning occur. Typically, the answer to this question is
in biology. But what do these terms mean? more active than we might expect.
4
Table 3. Correlation to the National Science Education Standards.
A. The Content Standards
Standard A: As a result of activities in grades 9–12, Correlation to Human
all students should develop abilities necessary to do scientific inquiry Genetic Variation
and understandings about scientific inquiry.
• Identify questions and concepts that guide scientific investigations. Lessons 1, 2 ,and 3
• Use technology and mathematics to improve investigations and communications. Lesson 2
• Formulate and revise scientific explanations and models using logic and evidence. Lessons 2 and 3
• Recognize and analyze alternative explanations and models. Lessons 2 and 3
• Communicate and defend a scientific argument. Lesson 3
• Understanding scientific inquiry. Lessons 2 and 3
Standard C: As a result of their activities in grades 9–12, Correlation to Human
all students should develop understanding of the cell and Genetic Variation
the molecular basis of heridity.
• Cells store and use information to guide their functions. Lessons 2, 3, and 5
• Cells can differentiate, and complex multicellular organisms are formed as a Lessons 2 and 5
highly organized arrangement of differentiated cells.
• In all organisms, the instructions for specifying the characteristics of the Lessons 2, 3, and 5
organism are carried in the DNA.
• Changes in DNA occur spontaneously at low rates. Lessons 2, 3, and 5
• Species evolve over time. Lesson 2
Standard E: As a result of activities in grades 9–12, Correlation to Human
all students should develop abilities of technological design and Genetic Variation
understandings about science and technology.
• Scientists in different disciplines ask different questions, use different Lesson 3
methods of investigation, and accept different types of evidence to support
these explanations.
• Science often advances with the introduction of new technologies. Lesson 5
• Creativity, imagination, and a good knowledge base are all required in the Lessons 1–5
work of science and engineering.
• Science and technology are pursued for different purposes. Lesson 5
Standard F: As a result of activities in grades 9–12, Correlation to Human
all students should develop understanding of Genetic Variation
• personal and community health. Lessons 2, 3, 4, and 5
• natural and human-induced hazards. Lessons 2, 3, 4, and 5
• science and technology in local, national, and global challenges. Lesson 5
Standard G: As a result of activities in grades 9–12, Correlation to Human
all students should develop understanding of Genetic Variation
• science as a human endeavor. Lesson 3
• nature of scientific knowledge. Lessons 1–5
• historical perspectives. Lesson 2
5
Implementing the Module
Human Genetic Variation
6
The activities in this module were designed with not involve students in active experimentation to
the following assumptions about active learning be fundamentally an inquiry experience.
(BSCS, 1999):
• An activity promotes active learning to the More than active or collaborative learning, inquiry-
degree to which all students, not simply a vocal based strategies attempt to teach students how
few, are involved in mental processing related biologists see the world, how they think about
to the content. what they see, and how they draw conclusions
• An activity promotes active learning to the that are consistent with observations and current
degree that it offers extended opportunities for knowledge. Such strategies say to the student, in
students to become personally engaged with effect, “This is science as a way of knowing.”
the content.
• An activity promotes active learning to the The BSCS 5E Instructional Model
degree that it involves students in thinking The lessons in the module were designed using
deeply about content. an instructional model to organize and sequence
the experiences offered to students. This model,
The activities also make extensive use of called the BSCS 5E Instructional Model, is based
collaborative learning. Most often occurring on constructivism, a term that expresses a view
within the context of group work, collaborative of the student as an active agent who “constructs”
and cooperative learning currently enjoy “favorite meaning out of his or her interactions with events
child” status among the many strategies available (Perkins, 1992). According to this view, rather
to teachers. than passively absorbing information, the student
redefines, reorganizes, elaborates, and changes his
Teachers are using group approaches across or her initial understandings through interactions
disciplines, for in- and out-of-class assignments, with phenomena, the environment, and other
with large and small classes, and with beginning individuals. In short, the student interprets
and advanced students. In fact, you will often find objects and phenomena and then internalizes this
that collaborative activities go hand-in-hand with interpretation in terms of previous experiences.
active learning.
A constructivist view of learning recognizes that
Collaborative learning and cooperative learning, the development of ideas and the acquisition of
which have long theoretical and empirical lasting understandings take time and experience
histories, come out of different academic (Saunders, 1992). In the typical classroom, this
traditions, operate on different premises, and means that fewer concepts and subjects can be
use different strategies. But both approaches covered during the school year or, in this case,
share a fundamental commitment to the notion in five days of instruction. Nevertheless, research
that students learn from and with each other— suggests that students who are given time and
“learning through joint intellectual effort,” opportunity to thoroughly grasp a small number
according to one expert (Brody, 1995, p. 134). In of important concepts do better on traditional
the interest of brevity, we will leave undiscussed tests than students who are exposed briefly to a
the finer distinctions between the two, offering large number of ideas (Sizer, 1992; Knapp et al.,
in this curriculum a mix of strategies that put 1995). In fact, the intensive thinking involved
students together and engage them in tasks that in constructing a thorough understanding of a
encourage learning together. few major ideas appears to benefit all students,
regardless of ability.
Finally, the activities in the module use inquiry-
based strategies. All truly inquiry-based activities Table 4 illustrates the key components of the
share the characteristics of active learning. In BSCS 5E Instructional Model, so-called because
addition, inquiry-based strategies emphasize it takes students through five phases of learning
discovery: the process of observation, followed by that are easily described using five words that
analysis, that leads to explanation, to conclusion, begin with the letter “E”: Engage, Explore,
or to the next question. Note that an activity need Explain, Elaborate, and Evaluate.
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Implementing the Module
Human Genetic Variation
Table 4. The key components of the BSCS 5E Model: What the teacher does.
Phase What the teacher does that’s What the teacher does that’s
consistent with the 5E Model inconsistent with the 5E Model
Engage • Creates interest • Explains concepts
• Generates curiosity • Provides definitions and answers
• Raises questions • States conclusions
• Elicits responses that uncover what students • Provides premature answers to
know or think about the concept or subject students’ questions
• Lectures
Explore • Encourages students to work together • Provides answers
without direct instruction from teacher • Tells or explains how to work through
• Observes and listens to students as they the problem
interact • Tells students they are wrong
• Asks probing questions to redirect students’ • Gives information or facts that solve
investigations when necessary the problem
• Provides time for students to puzzle • Leads students step-by-step to a
through problems solution
• Acts as a consultant for students
Explain • Encourages students to explain concepts • Accepts explanations that have no
and definitions in their own words justification
• Asks for justification (evidence) and • Neglects to solicit students’
clarification from students explanations
• Formally provides definitions, explanations, • Introduces unrelated concepts or skills
and new labels
• Uses students’ previous experiences as the
basis for explaining concepts
Elaborate • Expects students to use formal labels, • Provides definitive answers
definitions, and explanations provided • Tells students they are wrong
previously • Lectures
• Encourages students to apply or extend • Leads students step-by-step to a
concepts and skills in new situations solution
• Reminds students of alternative • Explains how to work through the
explanations problem
• Refers students to existing data and
evidence and asks, “What do you already
know?” “Why do you think ... ?”
Evaluate • Observes students as they apply new • Tests vocabulary words, terms, and
concepts and skills isolated facts
• Assesses students’ knowledge and/or skills • Introduces new ideas or concepts
• Looks for evidence that students have • Creates ambiguity
changed their thinking or behaviors • Promotes open-ended discussion
• Allows students to assess their own learning unrelated to concept or skill
and group-process skills
• Asks open-ended questions, such as,
“Why do you think . . . ?” “What evidence
do you have?” “What do you know
about x?” “How would you explain x?”
8
Table 5. The key components of the BSCS 5E Model: What the students do.
Phase What the students do that is What the students do that is
consistent with the 5E Model inconsistent with the 5E Model
Engage • Become interested in and curious about the • Ask for the “right” answer
concept/topic • Offer the “right” answer
• Express current understanding of a concept • Insist on answers or explanations
or idea • Seek closure
• Raise questions such as, What do I already
know about this? What do I want to know
about this? How could I find out?
Explore • “Mess around” with materials and ideas • Let others do the thinking and
• Conduct investigations in which they exploring (passive involvement)
observe, describe, and record data • Work quietly with little or no
• Try different ways to solve a problem or interaction with others (only
answer a question appropriate when exploring ideas or
• Acquire a common set of experiences so feelings)
they can compare results and ideas • Stop with one solution
• Compare their ideas with those of others • Demand or seek closure
Explain • Explain concepts and ideas in their own • Propose explanations from “thin
words air” with no relationship to previous
• Base their explanations on evidence experiences
acquired during previous investigations • Bring up irrelevant experiences and
• Become involved in student-to-student con- examples
versations in which they debate their ideas • Accept explanations without
• Record their ideas and current justification
understanding • Ignore or dismiss other plausible
• Reflect on and perhaps revise their ideas explanations
• Express their ideas using appropriate scien- • Propose explanations without evidence
tific language to support their ideas
• Compare their ideas with what scientists
know and understand
Elaborate • Make conceptual connections between new • Ignore previous information or
and former experiences evidence
• Use what they have learned to explain a • Draw conclusions from “thin air”
new object, event, organism, or idea • Use terminology inappropriately and
• Use scientific terms and descriptions without understanding
• Draw reasonable conclusions from evidence
and data
• Communicate their understanding to others
Evaluate • Demonstrate what they understand about • Disregard evidence or previously
the concept(s) and how well they can accepted explanations in drawing
implement a skill conclusions
• Compare their current thinking with that of • Offer only yes-or-no answers or
others and perhaps revise their ideas memorized definitions or explanations
• Assess their own progress by comparing as answers
their current understanding with their prior • Fail to express satisfactory explanations
knowledge in their own words
• Ask new questions that take them deeper • Introduce new, irrelevant topics
into a concept or topic area
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Implementing the Module
Human Genetic Variation
Explore Evaluate
Lesson 2, The Meaning of Genetic Variation, Finally, Lesson 5, Making Decisions in the Face
serves in a broad sense as the Explore phase of Uncertainty, acts as the Evaluate lesson for
of the model. In this lesson, students ask the program. At this point, it is important
and answer questions about the ways human that students see that they can use their
variation might be significant and then use understanding of human genetic variation in
resources on the curriculum’s Web site or in the real world. It is also important that they
the print materials provided to explore the receive some feedback on the adequacy of
significance of genetic variation as the basis their explanations and understandings.
for evolution by natural selection.
10
Evaluate lessons are complex and challenging, version of the sleep supplement that was very
and Lesson 5 will stretch your students’ abilities closely aligned with the theoretical underpinnings
to listen, think, and speak. of the BSCS 5Es. For the control group, the
teacher used a set of lessons based on the science
What’s the Evidence for the content of the sleep supplement but aligned with
Effectiveness of the BSCS 5E the most commonplace instructional strategies
Instructional Model? found in U.S. science classrooms (as documented
Support from educational research studies for by Horizon Research; Weiss et al., 2003). Both
teaching science as inquiry is growing (for groups had the same master teacher.
example, Geier et al., 2008; Hickey et al., 1999;
Lynch et al., 2005; and Minner et al., 2009). A Students taught with the BSCS 5Es and
2007 study, published in the Journal of Research an inquiry-based approach demonstrated
in Science Teaching (Wilson et al., 2010), is significantly higher achievement for a range
particularly relevant to the Human Genetic of important learning goals, especially when
Variation supplement. the results were adjusted for variance in pretest
scores. The results were also consistent across
In 2007, with funding from NIH, BSCS conducted time (both immediately after instruction and
a randomized, controlled trial to assess the four weeks later). Improvements in student
effectiveness of the BSCS 5Es. The study used learning were particularly strong for measures
an adaptation of the NIH supplement Sleep, Sleep of student reasoning and argumentation. The
Disorders, and Biological Rhythms, developed by following chart (Table 6) highlights some of
BSCS in 2003. Sixty high school students and one the study’s key findings. The results of the
teacher participated. The students were randomly experiment strongly support the effectiveness
assigned to the experimental or the control group. of teaching with the BSCS 5Es.
In the experimental group, the teacher used a
11
Implementing the Module
Human Genetic Variation
Evidence also suggests that the BSCS 5Es are An assessment icon and a description
effective in changing students’ attitudes on of what you can assess appear in
important issues. In a research study conducted the margin beside each embedded
during the field test for the NIH curriculum assessment.
supplement The Science of Mental Illness, BSCS
partnered with researchers at the University of How Can Controversial Topics Be
Chicago and the National Institute of Mental Handled in the Classroom?
Health. The study investigated whether a short- Teachers sometimes feel that the discussion of
term educational experience would change values is inappropriate in the science classroom
students’ attitudes about mental illness. The or that it detracts from the learning of “real”
results showed that after completing the science. The lessons in this module, however,
curriculum supplement, students stigmatized are based on the conviction that there is much
mental illness less than they had beforehand. to be gained by involving students in analyzing
The decrease in stigmatizing attitudes was issues of science, technology, and society.
statistically significant (Corrigan et al., 2007; Society expects all citizens to participate in
Watson et al., 2004). the democratic process, and our educational
system must provide opportunities for students
How Does the Module Support to learn to deal with contentious issues with
Ongoing Assessment? civility, objectivity, and fairness. Likewise,
Because we expect this module to be used in students need to learn that science intersects
a variety of ways and at a variety of points in with life in many ways.
an individual teacher’s curriculum, we believe
the most appropriate mechanism for assessing In this module, students have a variety of
student learning is one that occurs informally opportunities to discuss, interpret, and evaluate
at various points within the activities, rather basic science and public health issues in the
than something that happens more formally, just light of values and ethics. Many issues that
once at the end of the module. Accordingly, we students will encounter—especially those
have integrated a variety of specific assessment having to do with individual susceptibility to
components throughout the lessons. These disease and personal decisions that various
embedded assessment opportunities include people might make about genetic testing and
one or more of the following strategies: medical treatment—are potentially controversial.
• performance-based activities (for example, How much controversy develops will depend
structured discussions of potentially on many factors, such as how similar your
controversial issues); students are with respect to socioeconomic
• oral presentations to the class (for example, status, perspectives, value systems, and religious
role playing); and preferences. It will also depend on how you
• written assignments (for example, answering handle your role as facilitator. Your language
questions or writing magazine or newspaper and attitude factor into the flow of ideas and
articles, letters, and short reports). the quality of exchange among the students.
These strategies allow you to assess a variety of The following guidelines may help you think
aspects of the learning process, such as students’ about how to guide your students in discussions
prior knowledge and current understanding, that balance factual information with values.
problem-solving and critical-thinking skills, • Remain neutral. Neutrality may be the single
level of understanding of new information, most important characteristic of a successful
communication skills, and ability to synthesize discussion facilitator.
ideas and apply understanding to a new situation.
12
• Encourage your students to discover as much • Acknowledge all contributions in the same
information about the issue as possible. Ask evenhanded manner. If the class senses that
questions that help your students distinguish you favor one idea over another, you will
between those components of an idea or issue inhibit open debate and discussion. For
that scientific research can answer and those example, avoid praising the substance or
that are a matter of values. Maintaining this content of comments. Instead, acknowledge
distinction is particularly important as the willingness of students to contribute by
students discuss the issues about genetic making comments such as, “Thanks for that
testing raised in Lesson 5. Students should idea” or “Thanks for those comments.” As you
understand the importance of accurate display an open attitude, a similarly accepting
information to any discussion and should climate will begin to develop within the class.
recognize the importance of distinguishing • Create a sense of freedom in the classroom.
factual information from opinions. Remind students, however, that freedom
• Keep the discussion relevant and moving implies the responsibility to exercise that
forward by questioning or posing appropriate freedom in ways that generate positive
problems or hypothetical situations. Encourage results for all.
everyone to contribute, but do not force • Insist on a nonhostile environment in the
reluctant students into the discussion. classroom. Help your students learn to
• Emphasize that everyone must be open to respond to ideas instead of to the individuals
hearing and considering diverse views. presenting those ideas.
• Use unbiased questioning to help students • Respect silence. Reflective discussions
critically examine all views presented. are often slow. If you break the silence,
• Allow for the discussion of all feelings your students may allow you to dominate
and opinions. the discussion.
• Avoid seeking consensus on all issues. • Finally, at the end of the discussion, ask
This is particularly important in Lesson 5. your students to summarize the points
The multifaceted issues that the students they and their classmates have made. Let
discuss result in the presentation of divergent students know that your respect for them
views, and students should learn that this does not depend on their opinion about
is acceptable. any controversial issue.
• Keep your own views out of the discussion.
If your students ask what you think, you may
wish to respond with a statement such as,
“My personal opinion is not important here.
We want to consider your views.”
13
Implementing the Module
Using the Student Lessons
The heart of this module is the set of five lessons, In Advance provides instructions for collecting the
which we hope will carry important concepts materials, photocopying, and other preparations
related to disease and public health to your needed for the activities in the lesson.
students. To review the concepts in detail, refer
to Table 1 in “Implementing the Module” (page 3). Procedure outlines the lesson’s steps and provides
implementation suggestions and answers to
Format of the Lessons questions. Annotations in the margins, identified
As you scan the lessons, you will find that each by icons, provide specific hints about
contains several major features.
helping students see connections
At a Glance gives you a convenient summary between basic science and personal
of the lesson. and public health,
• The Overview provides a short summary
of what students do. assessing student understanding,
• Major Concepts states the central idea(s) and
the lesson is designed to convey.
• Objectives list three to five specific
understandings or abilities students should focusing students’ attention on the
have after completing the lesson. lesson’s major concepts during its
• Prerequisite Knowledge alerts you to the closing steps.
understandings and skills students should
have before beginning the lesson. Other icons indicate
• The Basic Science–Health Connection
describes how the lesson illustrates the when to use the Web site (see “Using
relationship between basic science and personal the Web Site” for instructions; a
and public health. The mission of NIH is print-based alternative is provided for
to “uncover new knowledge that will lead classes that don’t have access to the
to better health for everyone.” This mission Internet) and
statement recognizes that basic science and
personal and public health are not separate the beginning of a print-based
issues; they are not even two sides of one issue. alternative version.
Rather, they are inextricably linked and form
a powerful whole: Research into the basic
processes of life leads inevitably to strategies Potential Extensions describes ways you can
for improving health, and questions about extend or enrich the lesson.
health trigger research into basic processes.
• The Introduction places the lesson in a
context and provides a short overview of
its key components.
15
Human Genetic Variation
16
Using the Web Site
Hardware and Software Requirements If you are teaching all five lessons as a unit,
The Web site can be accessed with any computer we recommend that you keep your students
browser. Adobe Flash Player should be installed in the same collaborative groups for all the
on the hard drive of each computer that will activities. This will allow each group to develop
access the site. It’s freely available at http://get. a shared experience with the Web site and
adobe.com/flashplayer/. with the ideas and issues the activities present.
A shared experience will also enhance your
Getting the Most out of the Web Site students’ perceptions of the lessons as a
The ideal use of the Web site requires one conceptual whole. This will be particularly
computer for each student group. However, if you important in the activities toward the end
have only one computer available, you still can of the module, as students consider some of
use the site. For example, you can use a projection the ethical and logistical complexities associated
system to display the monitor image for the whole with our growing knowledge about human
class. If you do not have access to the Web site, genetic variation.
you can use the print-based alternative provided
for each Web activity. If your student-to-computer ratio is greater than
six students to one computer, you will need to
17
Human Genetic Variation
change the way you teach the module from the Web Activities for People with Disabilities
instructions in the lessons. For example, if you The Office of Science Education provides access
have only one computer available, you may want to the Curriculum Supplement Series for people
students to complete the Web-based work over with disabilities. The online versions of this series
an extended time period. You can do this several comply with Section 508 of the Rehabilitation Act.
ways. The most practical one is to use your If you use assistive technology (such as a Braille
computer as a center along with several other or screen reader) and have trouble accessing
centers at which students complete other activities. any materials on our Web site, please let us
In this approach, students rotate through the know. We’ll need a description of the problem,
computer center, eventually completing the the format in which you would like to receive
Web-based work you have assigned. the material, the Web address of the requested
material, and your contact information.
A second way to structure the lessons if you only
have one computer available is to use a projection Contact us at
system to display the computer monitor onto a Curriculum Supplement Series
screen for the whole class to see. Giving selected Office of Science Education
students in the class the opportunity to manipulate National Institutes of Health
the Web activities in response to suggestions and 6100 Executive Boulevard, Suite 3E01
requests from the class can give students some of Bethesda, MD 20892-7520
the same autonomy in their learning they would or
have gained from working in small groups. supplements@science.education.nih.gov
18
Understanding Human Genetic Variation
Genetics is the scientific study of inherited knowledge about human sex chromosomes that
variation. Human genetics, then, is the scientific was gained through the study of patients with
study of inherited human variation. sex chromosome abnormalities. A more current
example is our rapidly increasing understanding
Why study human genetics? One reason is simply of the mechanisms that regulate cell growth and
to understand ourselves better. As a branch reproduction, which we have gained primarily
of genetics, human genetics concerns itself through a study of genes that, when mutated,
with what most of us consider to be the most increase the risk of cancer.
interesting species on earth: Homo sapiens. But
our interest in human genetics does not stop at Likewise, the results of basic research inform
the boundaries of the species, for what we learn and stimulate research into human disease. For
about human genetic variation and its sources example, the development of recombinant DNA
and transmission inevitably contributes to our techniques (Figure 3) rapidly transformed the
understanding of genetics in general, just as the study of human genetics, ultimately allowing
study of variation in other species informs our
understanding of our own.
19
Human Genetic Variation
scientists to study the detailed structure and researchers to study DNA directly. Before the
functions of individual human genes, and to development of these techniques, scientists
manipulate these genes in a variety of previously studying human genetic variation were forced
unimaginable ways. to make inferences about molecular differences
from the phenotypes produced by mutant genes.
A third reason for studying human genetics is Furthermore, because the genes associated with
that it gives us a powerful tool for understanding most single-gene disorders are relatively rare,
and describing human evolution. At one time, they could be studied in only a small number
data from physical anthropology (including of families. Many of the traits associated with
information about skin color, body build, and these genes are also recessive and so could not be
facial traits) were the only source of information detected in people with heterozygous genotypes.
available to scholars interested in tracing human Unlike researchers working with other species,
evolutionary history. Today, however, researchers human geneticists are restricted by ethical
have a wealth of genetic data, including molecular considerations from performing experimental,
data, to draw on in their work. “at-will” crosses on human subjects. In addition,
human generations are on the order of 20 to
How Do Scientists Study Human 40 years, much too slow to be useful in classic
Genetic Variation? breeding experiments. All these limitations made
Two research approaches were historically identifying and studying genes in humans both
important in helping investigators understand tedious and slow.
the biological basis of heredity. The first,
transmission genetics, involved crossing In the past 60 years, however, beginning with
organisms and studying the offspring’s traits to the discovery of the structure of DNA and
develop hypotheses about the mechanisms of accelerating significantly with the development of
inheritance. This work demonstrated that in some recombinant DNA techniques in the mid-1970s,
organisms at least, heredity seems to follow a few a growing battery of molecular techniques has
definite and rather simple rules. made direct study of human DNA a reality. Key
examples of these techniques are
The second approach involved using cytologic • restriction analysis and molecular
techniques to study the machinery and processes recombination, which allow researchers
of cellular reproduction. This approach laid to cut and rejoin DNA molecules in
a solid foundation for the more conceptual highly specific and predictable ways;
understanding of inheritance that developed as • amplification techniques, such as the
a result of transmission genetics. By the early polymerase chain reaction (PCR), which
1900s, cytologists had make it possible to make unlimited copies
• demonstrated that heredity is the consequence of any fragment of DNA;
of the genetic continuity of cells by cell • hybridization techniques, such as fluorescence
division, in situ hybridization, which allow scientists to
• identified the gametes as the vehicles that compare DNA samples from different sources
transmit genetic information from one and to locate specific base sequences within
generation to another, and samples; and
• collected strong evidence for the central role of • the automated sequencing techniques that
the nucleus and the chromosomes in heredity. allowed workers to sequence the human
genome at an unprecedented rate.
As important as they were, the techniques of
transmission genetics and cytology were not One relatively new technique, DNA microarray
enough to help scientists understand human technology (also called DNA chip technology),
genetic variation at the level of detail now is a revolutionary tool designed to identify
possible. The central advantage that today’s mutations in genes or to survey expression of
molecular techniques offer is that they allow tens of thousands of genes in one experiment.
20
For an excellent review—with great illustrations— that many mRNA molecules hybridized to the
of how microarray technology is being used in gene and, therefore, that the gene is very active
medicine, see the article by Feero et al. (2010), in that cell type. Conversely, no fluorescence
listed in the References section. indicates that none of the cell’s mRNA molecules
hybridized to the gene and that the gene is
In one application of this technology, the chip is inactive in that cell type.
designed to detect mutations in a particular gene.
The DNA microchip consists of a small glass plate Although these technologies are still relatively
encased in plastic. It is manufactured using a new and are being used primarily for research,
process similar to the one used to make computer scientists expect that one day they will have
microchips. On its surface, it contains synthetic significant clinical applications. For example,
single-stranded DNA sequences identical to those DNA microarray technology has the potential to
of the normal gene and all possible mutations of significantly reduce the time and expense involved
that gene. To determine whether an individual in genetic testing. This technology or others like it
possesses a mutation in the gene, a scientist first may help make it possible to define an individual’s
obtains a sample of DNA from the person’s blood, risk of developing many types of hereditary cancer
as well as a sample of DNA from someone else that as well as other common disorders, such as heart
does not contain a mutation in that gene. After disease and diabetes. Likewise, scientists may
denaturing, or separating, the DNA samples into one day be able to classify human cancers by the
single strands and cutting them into smaller, more patterns of gene activity in the tumor cells and
manageable fragments, the scientist labels the then be able to design treatment strategies for
fragments with fluorescent dyes: the person’s DNA each specific type of cancer.
with red dye and the normal DNA with green dye.
How Much Genetic Variation Exists
Both sets of labeled DNA are allowed to hybridize, among Humans?
or bind, to the synthetic DNA on the chip. If the Homo sapiens is a relatively young species and
person does not have a mutation in the gene, both has not had as much time to accumulate genetic
DNA samples will hybridize equivalently to the variation as have the vast majority of species
chip and the chip will appear uniformly yellow. on Earth, most of which predate humans by
However, if the person does have a mutation, the enormous expanses of time. Nonetheless, there
mutant sequence on the chip will hybridize to is considerable genetic variation in our species.
the patient’s sample but not to the normal DNA, The human genome comprises about 3 × 109
causing the chip to appear red in that area. The base pairs of DNA, and the extent of human
scientist can then examine this area more closely genetic variation is such that no two humans,
to confirm that a mutation is present. save identical twins, ever have been or will be
genetically identical. Between any two humans,
DNA microarray technology is also allowing the amount of genetic variation—biochemical
scientists to investigate the activity in different individuality—is about 0.1 percent. This means
cell types of thousands of genes at the same time, that about 1 base pair out of every 1,000 will
an advance that will help researchers determine be different between any two individuals. Any
the complex functional relationships that exist two (diploid) people have about 6 × 106 base
between individual genes. This type of analysis pairs that are different, an important reason for
involves placing small snippets of DNA from the development of automated procedures for
hundreds or thousands of genes on a single analyzing genetic variation.
microscope slide, then allowing fluorescently
labeled mRNA molecules from a particular cell The most common polymorphisms (or genetic
type to hybridize to them. By measuring the differences) in the human genome are single-base-
fluorescence of each spot on the slide, scientists pair differences. Scientists call these differences
can determine how active various genes are in SNPs, for single-nucleotide polymorphisms. When
that cell type. Strong fluorescence indicates two different haploid genomes are compared,
21
Understanding Human Genetic Variation
Human Genetic Variation
SNP occurs, on average, about every 1,000 bases. Analysis of human genetic variation also
Other types of polymorphisms—for example, confirms that humans share much of their
differences in copy number, insertions, deletions, genetic information with the rest of the natural
duplications, and rearrangements—also occur but world—an indication of the relatedness of all
much less frequently. life by descent with modification from common
ancestors. The highly conserved nature of many
Notwithstanding the genetic differences genetic regions across considerable evolutionary
between individuals, all humans have a great distance is especially obvious in genes related
deal of their genetic information in common. to development. For example, mutations in the
These similarities help define us as a species. patched gene produce developmental abnormalities
Furthermore, genetic variation around the world in Drosophila, and mutations in the patched
is distributed in a rather continuous manner; homolog in humans produce analogous structural
there are no sharp, discontinuous boundaries deformities in the developing human embryo.
between human population groups. In fact,
research results consistently demonstrate that Geneticists have used the reality of evolutionary
about 85 percent of all human genetic variation conservation to detect genetic variations associated
exists within human populations, whereas about with some cancers. For example, mutations in the
only 15 percent of variation exists between genes responsible for repair of DNA mismatches
populations (Figure 4). That is, research reveals that arise during DNA replication are associated
that Homo sapiens is one continuously variable, with one form of colon cancer. These mismatched
interbreeding species. Ongoing investigation of repair genes are conserved in evolutionary history
human genetic variation has even led biologists all the way back to the bacterium Escherichia coli,
and physical anthropologists to rethink where the genes are designated mutL and mutS.
traditional notions of human racial groups. Geneticists suspected that this form of colon
cancer was associated with a failure of mismatch
repair, and they used the known sequences from
the E. coli genes to probe the human genome for
homologous sequences. This work led ultimately
to the identification of a gene associated with
increased risk for colon cancer.
22
Some genetic variation, however, can be positive, multiple genes and environmental variables. Such
providing an advantage in changing environments. diseases, therefore, are termed multifactorial. In
The classic example from the high school biology fact, the vast majority of human traits, diseases or
curriculum is the mutation for sickle hemoglobin, otherwise, are multifactorial.
which in the heterozygous state provides a selective
advantage in areas where malaria is endemic. The genetic distinctions between relatively rare
single-gene disorders and the more common
More recent examples include mutations in the multifactorial diseases are significant. Genetic
CCR5 gene that appear to provide protection variations that underlie single-gene disorders are
against AIDS. The CCR5 gene encodes a protein generally relatively recent, and they often have a
on the surface of human immune cells. HIV, the major, detrimental impact, disrupting homeostasis
virus that causes AIDS, infects immune cells by in significant ways. Such disorders also generally
binding to this protein and another protein on the exact their toll early in life, often before the end
surface of those cells. Mutations in the CCR5 gene of childhood. In contrast, the genetic variations
that alter its level of expression or the structure of that underlie common, multifactorial diseases
the resulting protein can decrease HIV infection. are generally of older origin and have a smaller,
Early research on one genetic variant indicates more gradual effect on homeostasis. Their onset is
that it may have risen to high frequency in generally in adulthood. The last two characteristics
northern Europe about 700 years ago, at about make the ability to detect genetic variations that
the time of the European epidemic of bubonic increase the risk of common diseases especially
plague. This finding has led some scientists to valuable because people have time to modify their
hypothesize that the CCR5 mutation may have behavior in ways that can reduce the likelihood
provided protection against infection by Yersinia that the disease will develop, even against a
pestis, the bacterium that causes plague. The fact background of genetic predisposition.
that HIV and Y. pestis both infect macrophages
supports the argument for a selective advantage How Is Our Understanding of Human
of this genetic variant. Genetic Variation Affecting Medicine?
As noted earlier, one of the benefits of
The sickle cell and AIDS-plague stories remind us understanding human genetic variation is its
that the biological significance of genetic variation practical value for understanding and promoting
depends on the environment in which genes are health and for understanding and combating
expressed. It also reminds us that differential disease. We probably cannot overestimate the
selection and evolution would not proceed in importance of this benefit. First, as Figure 5
the absence of genetic variation within a species. suggests, virtually every human disease has a
genetic component. In some diseases, such as
Some genetic variation is associated with disease, Huntington disease, Tay-Sachs disease, and cystic
of course, as classic single-gene disorders such as fibrosis, this component is very large. In other
sickle cell disease, cystic fibrosis, and Duchenne diseases, such as cancer, diabetes, and heart
muscular dystrophy remind us. Increasingly, disease, the genetic component is more modest.
research is also uncovering genetic variations In fact, we do not typically think of these
associated with diseases that are among the diseases as “genetic diseases,” because we
major causes of sickness and death in developed inherit not the certainty of developing a disease,
countries—diseases such as heart disease, cancer, but only a predisposition to developing it.
diabetes, and psychiatric disorders such as
schizophrenia and bipolar disorder (often called In still other diseases, the genetic component is
manic depression). Whereas disorders such as very small. The crucial point, however, is that
cystic fibrosis or Huntington disease result from it is there. Even infectious diseases, which we
the effects of mutation in a single gene and are have traditionally placed in a completely different
evident in virtually all environments, the more category from genetic disorders, have a real,
common diseases result from the interaction of albeit small, genetic component. For example,
23
Understanding Human Genetic Variation
Human Genetic Variation
Figure 5. Virtually all human diseases, including the three shown here, have a genetic component.
as the CCR5 example described earlier illustrates, increased risk for the disease and recognize
even AIDS is influenced by a person’s genotype. genotypic differences that have implications for
In fact, some people appear to have genetic effective treatment. At the other end are new
resistance to HIV infection as a result of carrying drug and gene therapies that specifically target
a variant of the CCR5 gene. the biochemical mechanisms that underlie the
disease symptoms or even replace, manipulate, or
Second, each of us is at some genetic risk and supplement nonfunctional genes with functional
thus can benefit, at least theoretically, from the ones. Indeed, as Figure 6 suggests, we are
progress scientists are making in understanding entering the era of molecular medicine.
and learning how to respond to these risks.
Scientists estimate that each of us has between 5 Genetic testing is not a new healthcare
and 50 mutations that carry some risk for disease strategy. Newborn screening for diseases like
or disability. Some of us may not experience phenylketonuria (PKU) has been going on
negative consequences from the mutations we for 40 years in many states. Nevertheless, the
carry, either because we do not live long enough remarkable progress scientists are making in
or because we may not be exposed to the relevant mapping and cloning human disease genes brings
environmental triggers. The reality, however, with it the prospect for the development of more
is that the potential for negative consequences genetic tests in the future. The availability of
from our genes exists for each of us. such tests can have a significant impact on the
way the public views a particular disease and
How is modern genetics helping us address the can also change the pattern of care that people
challenge of human disease? As Figure 6 shows, in affected families seek and receive. For example,
modern genetic analysis of a human disease the identification of the BRCA1 and BRCA2 genes
begins with mapping and cloning the associated and the demonstration that particular variants
gene or genes. Some of the earliest disease of these genes are associated with an increased
genes to be mapped and cloned were the genes risk of breast and ovarian cancer have paved
associated with Duchenne muscular dystrophy, the way for the development of guidelines and
retinoblastoma, and cystic fibrosis. More recently, protocols for testing individuals with a family
scientists have announced the cloning of genes history of these diseases. BRCA1, located on the
for breast cancer, diabetes, and Parkinson disease. long arm of chromosome 17, was the first to be
isolated, and variants of this gene account for
As Figure 6 also shows, mapping and cloning about 40 to 50 percent of all inherited breast
a disease-related gene opens the way for the cancer, or about 3 percent of all breast cancer.
development of a variety of new healthcare Variants of BRCA2, located on the long arm of
strategies. At one end of the spectrum are chromosome 13, appear to account for about
genetic tests intended to identify people at 20 to 30 percent of all inherited breast cancer.
24
Figure 6. How the Human Genome Project leads to better health care. Identifying genes related to disease can lead
to strategies that reduce the risk of disease (preventive medicine); guidelines for prescribing drugs based on a person’s
genotype (pharmacogenomics); procedures that alter the affected gene (gene therapy); or drugs aimed at the biological
mechanism that produces the disease symptoms (drug therapy). The Human Genome Project has accelerated the
development of these strategies.
Variants of these genes also slightly increase the drugs to work well in some people and less well,
risk for men of developing breast, prostate, or or with dangerous adverse reactions, in others.
possibly other cancers. For example, researchers investigating Alzheimer
disease have found that the way patients respond
Scientists estimate that hundreds of thousands of to drug treatment can depend on which of three
women in the United States have one of hundreds genetic variants of the ApoE (apolipoprotein E)
of significant mutations already detected in the gene a person carries. Likewise, some of the
BRCA1 gene. For a woman with a family history of variability in children’s responses to therapeutic
breast cancer, the knowledge that she carries one doses of albuterol, a drug used to treat asthma,
of the variants of BRCA1 or BRCA2 associated with was recently linked to genotypic differences in
increased risk can be important information. If the beta-2-adrenergic receptor. Because beta-2-
she does carry one of these variants, she and her adrenergic receptor agonists (of which albuterol
physician can consider several changes in her is one) are the most widely used agents in the
health care, such as increasing the frequency of treatment of asthma, these results may have
physical examinations, introducing mammography profound implications for understanding the
at an earlier age, and even having a prophylactic genetic factors that determine an individual’s
mastectomy. In the future, drugs may also be response to asthma therapy.
available that decrease the risk of developing
breast cancer. Experts predict that increasingly, physicians will
use genetic tests to match drugs to an individual
The ability to test for the presence in individuals patient’s body chemistry so they can prescribe
of particular gene variants is also changing the the safest and most effective drugs and dosages.
way drugs are prescribed and developed. A rapidly After identifying the genotypes that determine
growing field known as pharmacogenomics individual responses to particular drugs,
focuses on crucial genetic differences that cause pharmaceutical companies will likely set out to
25
Understanding Human Genetic Variation
Human Genetic Variation
develop new, highly specific drugs and revive Finally, the identification, cloning, and sequencing
older ones whose effects seemed, in the past, of a disease-related gene can open the door to the
too unpredictable to be of clinical value. development of strategies for treating the disease
that use the instructions encoded in the gene
Knowledge of the molecular structure of itself. Collectively referred to as gene therapy,
disease-related genes is also changing the way these strategies typically involve adding a copy
researchers approach developing new drugs. A of the normal variant of a disease-related gene
striking example followed the discovery in 1989 to a patient’s cells. The most familiar examples
of the gene associated with cystic fibrosis (CF). of this type of gene therapy are cases in which
Researchers began to study the function of the researchers use a vector to introduce the normal
normal and defective proteins involved in the variant of a disease-related gene into a patient’s
disease in order to understand the biochemical cells and then return those cells to the patient’s
consequences of the gene’s variant forms and to body to provide the function that was missing.
develop new treatment strategies based on that
knowledge. The normal protein, called CFTR This strategy was first used successfully to treat
(for cystic fibrosis transmembrane conductance inherited immune deficiencies. These diseases
regulator), is embedded in the membranes of were chosen because the mutant gene causing the
several cell types in the body, where it serves disease was known and there was evidence that
as a channel, transporting chloride ions out even a few corrected cells could restore complete
of the cells. In CF patients, depending on the immune function. Since 2000, 37 children
particular mutation the individual carries, the with either X-linked severe combined immune
CFTR protein may be reduced or missing from deficiency (X-SCID, the “Bubble Boy Disease”) or
the cell membrane or it may be present but ADA-SCID (deficiency of the adenosine deaminase
not functioning properly. In some mutations, enzyme that prevents the correct development
synthesis of CFTR protein is interrupted, and the and functioning of T-lymphocytes) have been
cells produce no CFTR molecules at all. treated with this approach. Bone marrow cells
from these patients were exposed to a virus
Although all the mutations associated with CF containing a normal copy of the mutant gene and
impair chloride transport, the consequences were then transplanted back into the patients.
for patients with different mutations vary. For To date, 33 of these 37 patients (89 percent) have
example, patients with mutations causing absent been cured. Two patients had very low rates of
or markedly reduced CFTR protein levels may gene transfer, one patient failed the bone marrow
have more severe disease than patients with transplant, and one patient died of an adverse
mutations in which CFTR is present but has event related to the gene therapy. In comparison,
altered function. The different mutations also the best conventional therapy for SCID is bone
suggest different treatment strategies. For example, marrow transplantation from a compatible donor.
the most common CF-related mutation (called delta If compatible bone marrow donors had been
F508) leads to the production of protein molecules available for these patients, only 65 percent
(called delta F508 CFTR) that are misprocessed would be expected to survive, so gene therapy
and degraded prematurely, before they reach the is the treatment of choice for these diseases.
cell membrane. This finding suggests that drug
treatments that would enhance transport of the Cancer presents a complicated problem for any
CFTR protein to the cell membrane or prevent treatment because the exact mutation causing
its degradation could yield important benefits the disease is not usually known and therapies
for patients with delta F508 CFTR. Such drug can injure the healthy cells surrounding the
strategies have been vigorously pursued by the tumor. Gene therapy is being used to treat a
Cystic Fibrosis Foundation, leading to clinical variety of cancers, however. One successful
trials of compounds that both assist protein strategy is to use gene therapy to modify the
processing and encourage proper functioning of body’s white blood cells so that they become
CFTR once it reaches the membrane. efficient killers of tumor cells. In one study,
26
patients with malignant lymphomas that had inception of the HGP, required more than eight
been resistant to all other therapies were treated years and $50 million. In contrast, now that the
with gene-modified white blood cells. More HGP is completed, finding a gene associated with
than three-quarters of the patients responded to a Mendelian disorder can be accomplished in just
the treatment, and 41 percent were completely weeks at a cost of less than $10,000.
cured of the disease. In another study, genetic
modifications were able to direct white blood Over the past few years, research into human
cells to another type of cancer: neuroblastoma, genetic variation has made the dramatic transition
a common childhood cancer with no effective from focusing primarily on genes associated with
treatment. The neuroblastoma tumors shrank or single-gene disorders, which are relatively rare
disappeared in half the patients. Because of the in the human population, to focusing on genes
specificity of these anticancer cells, there were associated with common multifactorial diseases.
no significant side effects. All told, more than Because these diseases are not rare, we can expect
1,000 patients have participated in cancer gene that this work will affect many more people.
therapy studies, and none of them has died as Understanding the genetic and environmental
a consequence of the gene therapy. Because of bases for these multifactorial diseases will also
the success of these studies, gene therapy is now lead to increased testing and the development
being used earlier in the treatment of cancer, of new interventions that will likely have an
when the prospects for a cure are better. enormous effect on the practice of medicine
in the next century.
Gene therapy is being developed for many other
diseases as well. Dogs have been cured of all Genetics, Ethics, and Society
these diseases by gene therapy: What are the implications of using our growing
• hemophilia, knowledge of human genetic variation to improve
• several enzyme deficiencies that slowly kill personal and public health? As noted earlier, the
brain and muscle cells because they store rapid pace of the discovery of genetic factors in
toxic substances, disease has improved our ability to predict the
• a third immune-deficiency disease, and risk of disease in asymptomatic individuals. We
• hereditary blindness. have learned how to prevent the manifestations
of some of these diseases, and we are developing
The success of these animal studies has allowed the capacity to treat others.
the therapies to be developed for humans with
the same diseases. A recent study of gene Yet, much remains unknown about the benefits
therapy for hereditary blindness has shown and risks of building an understanding of
vast improvement in the vision of the treated human genetic variation at the molecular level.
patients, and it is hoped that this result will While this information would have the potential
lead to effective gene therapy for other sight to dramatically improve human health, the
disorders such as glaucoma. architects of the HGP realized that it would also
raise a number of complex ethical, legal, and
As Figure 6 indicates, the Human Genome social issues. To anticipate and address these
Project (HGP) has significantly accelerated the issues, they established in 1990 the Ethical,
pace of both the discovery of human genes and Legal, and Social Implications (ELSI) program.
the development of new healthcare strategies This program, perhaps more than any other, has
based on knowledge of a gene’s structure and focused public attention, as well as the attention
function. The new knowledge and technologies of educators, on the increasing importance of
that emerged from HGP-related research have preparing citizens to understand and contribute
also reduced the cost of finding human genes. For to the ongoing public dialogue related to
example, the search for the gene associated with advances in genetics.
cystic fibrosis, which ended in 1989, before the
27
Understanding Human Genetic Variation
Human Genetic Variation
Ethics is the study of right and wrong, good and Second, ethics requires a solid foundation of
bad. It has to do with the actions and character of information and rigorous interpretation of that
individuals, families, communities, institutions, information. For example, one must have a solid
and societies. During the past two and one-half understanding of biology to evaluate the recent
millennia, Western philosophy has developed a decision by the Icelandic government to create a
variety of powerful methods and a reliable set of database that will contain extensive genetic and
concepts and technical terms for studying and medical information about the country’s citizens.
talking about the ethical life. Generally speaking, Knowledge of science is also needed to discuss
we apply the terms “right” and “good” to those the ethics of genetic screening or of germ line
actions and qualities that foster the interests of gene therapy. Ethics is not strictly a theoretical
individuals, families, communities, institutions, discipline but is concerned in vital ways with
and society. Here, an “interest” refers to a practical matters.
participant’s share or participation in a situation.
The terms “wrong” or “bad” apply to those Third, discussions of ethical issues often lead
actions and qualities that impair interests. to the identification of very different answers
to questions about what is right and wrong
Ethical considerations are complex and and good and bad. This is especially true in a
multifaceted, and they raise many questions. society such as our own, which is characterized
Often, there are competing, well-reasoned by diverse perspectives and values. Consider,
answers to questions about what is right and for example, the question of whether adolescents
wrong, and good and bad, about an individual’s should be tested for late-onset genetic conditions.
or a group’s conduct or actions. Typically, these Genetic-testing centers routinely withhold
answers all involve appeals to values. A value genetic tests for Huntington disease (HD) from
is something that has significance or worth in asymptomatic patients under the age of 18. The
a given situation. One of the exciting aspects rationale is that the condition expresses itself
of any ethics discussion is the variety of ways later in life and, at present, there is no treatment
the individuals involved assign values to things, for it. There is not necessarily an immediate,
persons, and states of affairs. Examples of values physical health benefit for a minor from a specific
that students may appeal to in a discussion diagnosis based on genetic testing. In addition,
about ethics include autonomy, freedom, privacy, there is concern about the psychological effects
sanctity of life, religion, protecting another of knowing that later in life one will get a
from harm, promoting another’s good, justice, debilitating, life-threatening condition. Teenagers
fairness, relationships, scientific knowledge, can wait until they are adults to decide what
and technological progress. and when they would like to know. On the
other hand, some argue that many adolescents
Acknowledging the complex, multifaceted and young children do have sufficient autonomy
nature of ethical discussions is not to suggest in consent and decision making and may wish
that “anything goes.” Experts generally agree to know their future. Others argue that parents
on the following features of ethics. First, ethics should have the right to have their children
is a process of rational inquiry. It involves tested because parents make many other
posing clearly formulated questions and seeking medical decisions on behalf of their children.
well-reasoned answers to those questions. This example illustrates how the tools of ethics
For example, we can ask questions about an can bring clarity and rigor to discussions
individual’s right to privacy regarding personal involving values.
genetic information; we can also ask questions
about the appropriateness of particular uses of One of the goals of this module is to help
gene therapy. Well-reasoned answers to such students see how understanding science can
questions constitute arguments. Ethical analysis help individuals and society make reasoned
and argument, then, result from successful decisions about issues related to genetics and
ethical inquiry. health. Lesson 5, Making Decisions in the Face
28
of Uncertainty, presents students with the case of dysfunction. Ethics provides a framework for
a woman who is concerned that she may carry identifying and clarifying values and the choices
an altered gene that predisposes her to breast that flow from these values. But the relationships
and ovarian cancer. The woman is faced with between scientific information and human
numerous decisions, which students also consider. choices, and between choices and behaviors,
Thus, the focus of Lesson 5 is prudential decision are not straightforward. In other words, human
making, which involves the ability to avoid choice allows individuals to choose against sound
unnecessary risk when it is uncertain whether knowledge, and choice does not require action.
an event will actually occur. By completing the
lesson, students understand that uncertainty is Nevertheless, it is increasingly difficult to
often a feature of questions related to genetics deny the claims of science. We are continually
and health, because our knowledge of genetics is presented with great amounts of relevant publicly
incomplete and constantly changing. In addition, accessible scientific and medical knowledge. As a
students see that making decisions about an consequence, we can think about the relationships
uncertain future is complex. In simple terms, among knowledge, choice, behavior, and human
students have to ask themselves, “How bad is the health in the following ways:
outcome and how likely is it to occur?” When
the issues are weighed, different outcomes are Knowledge (what is known and not known)
possible, depending on one’s estimate of the + Choice = Power
incidence of the occurrence and how much
burden one attaches to the risk. Power + Behavior = Enhanced Human Health
(that is, personal and public health)
Clearly, science and ethics both play important
roles in helping individuals make choices about One of the goals of this module is to encourage
individual and public health. Science provides students to think in terms of these relationships,
evidence that can help us understand and now and as they grow older.
treat human disease, illness, deformity, and
29
Understanding Human Genetic Variation
References
American Society of Human Genetics, American Geier, R., Blumenfeld, P.C., Marx, R.W., Krajcik,
College of Medical Genetics. 1995. Points to J.S., Fishman, B., Soloway, E., et al. 2008.
consider: Ethical, legal, and psychological Standardized test outcomes for students
implications of genetic testing in children and engaged in inquiry-based science curricula
adolescents. Journal of Human Genetics, 57: in the context of urban reform. Journal of
1233–1241. Research in Science Teaching, 45: 922–939.
Biological Sciences Curriculum Study. 1999. Green, E.D., Guyer, M.S., and the National Human
Teaching Tools. Dubuque, IA: Kendall/Hunt Genome Research Institute. 2011. Charting a
Publishing Company. course for genomic medicine from base pairs
to bedside. Nature, 470: 204–213.
Bonwell, C.C., and Eison, J.A. 1991. Active
Learning: Creating Excitement in the Harrison, G.A., Tanner, J.M., Pilbeam, D.R.,
Classroom. (ASHE-ERIC Higher Education and Baker, P.T. 1988. Human Biology: An
Report No. 1). Washington, DC: The George Introduction to Human Evolution, Variation,
Washington University: School of Education Growth, and Adaptability. New York: Oxford
and Human Development. University Press.
Brody, C.M. 1995. Collaborative or cooperative Hickey, D.T., Kindfeld, A.C.H., Horwitz, P., and
learning? Complementary practices for Christie, M.A. 1999. Advancing educational
instructional reform. The Journal of Staff, theory by enhancing practice in a technology
Program, and Organizational Development, supported genetics learning environment.
12(3): 134–143. Journal of Education, 181: 25–55.
Collins, F.S., Patrinos, A., Jordan, E., Chakravarti, Knapp, M.S., Shields, P.M., and Turnbull, B.J.
A., Gesteland, R., and Walters, L. 1998. New 1995. Academic challenge in high-poverty
goals for the U.S. Human Genome Project: classrooms. Phi Delta Kappan, 76(10):
1998–2003. Science, 282(5389): 682–689. 770–776.
Collins, G.S., and Barker, A.D. 2007. Mapping Lander, E.S. 1999, January. Array of hope.
the cancer genome. Scientific American, Supplement to Nature Genetics, 21.
296: 50–57.
Lazarou, J., Pomeranz, B.H., and Corey, P.N. 1998,
Corrigan, P., Watson, A., Otey, E., Westbrook, April 15. Incidence of adverse drug reactions
A., Gardner, A., Lamb, T., et al. 2007. How in hospitalized patients. Journal of the
do children stigmatize people with mental American Medical Association, 279: 1200–1205.
illness? Journal of Applied Social Psychology,
37(7): 1405–1417. Lynch, S., Kuipers, J., Pyke, C., and Szesze, M.
2005. Examining the effects of a highly rated
Feero, W.G., Guttmacher, A.E., and Collins, F.S. science curriculum unit on diverse students:
2010. Genomic medicine—an updated Results from a planning grant. Journal of
primer. New England Journal of Medicine, Research in Science Teaching, 42: 921–946.
362: 2001–2011.
31
Human Genetic Variation
Mange, E.J., and Mange, A.P. 1999. Basic Human Rennie, J., and Rusting, R. 1996, September.
Genetics, 2nd ed. Sunderland, MA: Sinauer Making headway against cancer. Scientific
Associates, Inc. American, 275(3): 56.
Martinez, F.D., Graves, P.E., Baldini, M., Solomon, Roblyer, M.D., Edwards, J., and Havriluk, M.A.
S., and Erickson, R. 1997, December. 1997. Integrating Educational Technology
Association between genetic polymorphisms into Teaching. Upper Saddle River, NJ:
of the 2-adrenoceptor and response to Prentice-Hall, Inc.
albuterol in children with and without a
history of wheezing. Journal for Clinical Saltus, R. 1998, April 20. Tailor-made drugs.
Investigation, 100(12): 3184–3188. The Boston Globe.
Minner, D.D., Jurist Levy, A., and Jeanne Century, Saunders, W.L. 1992. The constructivist
J. 2009. Inquiry-based science instruction— perspective: Implications and teaching
What is it and does it matter? Results from strategies for science. School Science and
a research synthesis years 1984 to 2002. Mathematics, 92(3): 136–141.
Journal of Research in Science Teaching,
published online at Wiley InterScience Sizer, T.R. 1992. Horace’s School: Redesigning
(www.interscience.wiley.com). the American High School. New York:
Houghton Mifflin Co.
Moore, J.A. 1993. Science as a Way of Knowing:
The Foundations of Modern Biology. Cambridge, Vogel, F., and Motulsky, A.G. 1997. Human
MA: Harvard University Press. Genetics: Problems and Approaches, 3rd ed.
New York: Springer.
National Human Genome Research Institute
Web site. http://www.nhgri.nih.gov. Watson, A.C., Otey, E., Westbrook, A.L., Gardner,
A.L., Lamb, T.A., Corrigan, P.W., et al.
National Institutes of Health. 1996. Congressional 2004. Changing middle schoolers’ attitudes
Justification. Bethesda, MD. about mental illness through education.
Schizophrenia Bulletin, 30(3): 563–572.
National Research Council. 1996. National
Science Education Standards. Washington, DC: Weiss, I.R., Pasley, J.D., Smith, P.S., Banilower,
National Academy Press. E.R., and Heck, D.J. 2003. Looking Inside the
Classroom: A Study of K–12 Mathematics and
Perkins, D. 1992. Smart Schools: Better Thinking Science Education in the U.S. Chapel Hill, NC:
and Learning for Every Child. New York: Horizon Research.
The Free Press.
Wilson, C.D., Taylor, J.A., Kowalski, S.M., and
Project Kaleidoscope. 1991. What Works: Carlson, J. 2010. The relative effects and
Building Natural Science Communities, equity of inquiry-based and commonplace
Volume 1. Washington, DC: Stamats science teaching on students’ knowledge,
reasoning, and argumentation. Journal of
Communications, Inc.
Research in Science Teaching, 47(3), 276–301.
32
Additional Resources
for Teachers
Online Genetics Education Resources GeneTests
http://www.genetests.org/
Access Excellence Information for health professionals about
http://www.accessexcellence.org hundreds of genetic tests.
A series of learning modules on multiple science
and health topics, including biotech and genetics. Genetic Science Learning Center
Sponsored by the National Health Museum, a http://learn.genetics.utah.edu/
nonprofit organization founded by former U.S. From the Eccles Institute of Human Genetics
Surgeon General C. Everett Koop. at the University of Utah, a Web site created
to help people understand how genetics affects
American Medical Association: Family their lives and society.
History Tools
http://www.ama-assn.org/ama/pub/category/2380.html Genetics and Molecular Medicine
Tools for gathering family history. (American Medical Association)
http://www.ama-assn.org/ama/pub/category/1799.html
The DNA Files Links to current articles and other resources.
http://www.dnafiles.org/
A series of 14 one-hour public radio Genetics Education Center
documentaries and related information. http://www.kumc.edu/gec
A comprehensive listing of genetics education
Dolan DNA Learning Center resources, including networking sites,
http://www.dnalc.org/ documentary films, lectures, booklets,
Dolan’s mission is to prepare students and activities, and programs. Compiled by the
families to thrive in the gene age, envisioning Genetics Education Center, University of
a day when all elementary students are exposed Kansas Medical Center.
to principles of genetics and disease risk; when
all high school students have the opportunity to Genetics Home Reference
do hands-on experiments with DNA; and when http://ghr.nlm.nih.gov
all families have access to genetic information Provides consumer information about genetic
they need to make informed healthcare choices. conditions and the genes or chromosomes
Includes an interactive DNA timeline. responsible for those conditions.
33
Human Genetic Variation
34
DNA Patent Database Family Medical History and Tools
http://dnapatents.georgetown.edu Resources Online
Searchable database of U.S. DNA-based
patents issued by the U.S. Patent and My Family Health Portrait
Trademark Office (USPTO). (Web Version Only)
https://familyhistory.hhs.gov/fhh-web/home.action
The Council for Responsible Genetics The Web-based tool from the U.S. Surgeon
http://www.gene-watch.org General’s Family History Initiative for use
Information on the social, ethical, on any computer with an Internet connection
and environmental implications of and a Web browser.
genetic technologies.
My Family Health Portrait
Genethics.ca (downloadable tool and Web version)
http://www.genethics.ca/ http://www.hhs.gov/familyhistory/portrait/index.html
Information on the social, ethical, and policy The original 2004 tool from the U.S. Surgeon
issues associated with genetic and genomic General’s Family History Initiative to download
knowledge and technology. and use on your computer.
Genetics and Public Policy Center National Society for Genetic Counselors:
http://www.dnapolicy.org Family History Tool
Information on genetic technologies and genetic http://www.nsgc.org/About/FamilyHistoryTool/
policies for the public, media, and policymakers. tabid/226/Default.aspx
Information on collecting family health history.
HumGen International
http://www.humgen.org/int/index_lang.cfm?lang=1 Genetic Counseling, Support, and
Access to a comprehensive international Advocacy Groups Online
database on the legal, social, and ethical
aspects of human genetics. Coalition for Genetic Fairness
http://www.geneticfairness.org/index.html
National Information Resources on Advocacy group for federal legislation regarding
Ethics and Human Genetics genetics discrimination through the National
http://bioethics.georgetown.edu/nirehg/ Partnership for Women and Families.
Links to resources on ethics and human genetics.
Find a Genetic Counselor
National Human Genome Research http://www.nsgc.org/FindaGeneticCounselor/tabid/64/
Institute ELSI Research Program Default.aspx
http://www.genome.gov/ A searchable database of genetics counseling
Information, articles, and links on a wide range services. Search by location, name, institution,
of ethical, legal, and social issues from NHGRI. type of practice, or specialty. Hosted by the
National Society of Genetic Counselors.
The President’s Council on Bioethics
http://www.bioethics.gov GeneTests: Clinic Directory
Information on current bioethical issues. http:// http://www.ncbi.nlm.nih.gov/sites/GeneTests/
clinic?db=genetests
Database of genetics clinics, searchable by
location, population served, and specialty.
35
Additional Resources for Teachers
Human Genetic Variation
36
Screening, Testing, and Risk of diseases have spurred debate on the
Assessment Resources Online interplay of “race,” “ethnicity,” genetics, and
health. Collins examines this complex issue in
National Birth Defects a commentary in the journal Nature Genetics.
Prevention Network http://www.genome.gov/Pages/News/Documents/
http://www.nbdpn.org RaceandGeneticsCommentary.pdf
Network of birth-defect care providers. • Race and ethnicity in the Genome Era: The
complexity of the constructs, January 6, 2005.
National Cancer Institute: An article written as part of a January 2005
Breast Cancer Risk Assessment Tool special issue of the American Psychologist
http://bcra.nci.nih.gov/brc/ entitled Genes, Race and Psychology in the
Interactive tool to measure a woman’s risk of Genome Era. The series of 10 articles from
invasive breast cancer. scholars who work in the fields of genetics,
race, or related areas was created to begin a
National Newborn Screening and discussion of the issue of race and genetics
Genetics Resource Center within the field of psychology. Published by
http://genes-r-us.uthscsa.edu/ the American Psychological Association. http://
Clinical genetics and newborn screening. www.apa.org/journals/releases/amp6019.pdf
• Realizing the promise of genomics in
Understanding Cancer Series: biomedical research, November 23, 2005.
Gene Testing An article by Collins and NIH Deputy
http://www.cancer.gov/cancertopics/ Director Alan Guttmacher, who discuss the
understandingcancer/genetesting/ future of biomedical research, from creating
Primer on genetic testing from the National the haplotype map to explore variation,
Cancer Institute (NCI). to successfully integrating genomics into
health care. From the Journal of the American
Selected References about Genetic Medical Association. http://www.genome.
Variation by NIH Scientists gov/26525022#2005
• Human Genome Collection, June 5,
Francis S. Collins, M.D., Ph.D., 2006. Nature presents the complete and
Director, NIH comprehensive DNA sequence of the human
• The Genome Era and mental illness, Summer/ genome as a freely available resource, plus
Fall 2003. Reprinted with permission from new commentary by Collins, past Department
the NAMI Advocate. You may also wish to of Energy Director Ari Patrinos, and former
read the introductory article published in the Director of the Sanger Centre John Sulston,
same issue, by Laura Lee Hall, Ph.D., Senior among others. http://www.nature.com/nature/
Research Director, NAMI, The start of a real supplements/collections/humangenome/index.html
revolution: genetics and psychiatric illness. • Mapping the cancer genome, March 2007. In
http://www.genome.gov/Pages/News/Documents/ this issue of Scientific American, Collins and
GenomeMental.pdf Deputy Director for Advanced Technologies
• Genomics: The coming revolution in medicine. and Strategic Partnerships of the National
From Global Agenda, the magazine of the Cancer Institute Anna D. Barker find that
World Economic Forum Annual Meeting 2003. pinpointing the genes involved in cancer will
http://www.genome.gov/Pages/News/Documents/ help chart a new course across the complex
GlobalAgenda.pdf landscape of human malignancies. http://www.
• What we do and don’t know about ‘race,’ scientificamerican.com/article.cfm?id=mapping-
‘ethnicity,’ genetics and health at the dawn of the-cancer-genome
the genome era, November 14, 2004. Recent
advances in the understanding and treatment
37
Additional Resources for Teachers
Human Genetic Variation
38
Glossary
The following glossary is from the Talking homozygous for that gene. If the alleles are
Glossary on the National Human Genome different, the individual is heterozygous. Though
Research Institute’s Web site, available at the term “allele” was originally used to describe
http://www.genome.gov/glossary. variation among genes, it now also refers to
variation among noncoding DNA sequences.
ACGT: ACGT is an acronym for the four types
of bases found in a DNA molecule: adenine (A), amino acids: Amino acids are a set of 20
cytosine (C), guanine (G), and thymine (T). A different molecules used to build proteins.
DNA molecule consists of two strands wound Proteins consist of one or more chains of amino
around each other, with each strand held together acids called polypeptides. The sequence of the
by bonds between the bases. Adenine pairs with amino acid chain causes the polypeptide to fold
thymine, and cytosine pairs with guanine. The into a biologically active shape. The amino acid
sequence of bases in a portion of a DNA molecule, sequences of proteins are encoded in the genes.
called a gene, carries the instructions needed to
assemble a protein. ancestry-informative markers: Ancestry-
informative markers are sets of polymorphisms
acquired immunodeficiency syndrome (AIDS): for a particular DNA sequence that appear in
AIDS is a collection of symptoms known as substantially different frequencies between
acquired immunodeficiency syndrome. It is caused populations from different geographical regions
by infection with the human immunodeficiency of the world. Ancestry-informative markers can
virus (HIV), which leads to loss of immune cells be used to estimate the geographical origins of
and leaves individuals susceptible to other infections the ancestors of an individual typically by
and the development of certain types of cancers. continent of origin (Africa, Asia, or Europe).
There is no cure for AIDS, though drugs can slow
down and stabilize the disease’s progress. animal model: An animal model is a nonhuman
species used in medical research because it can
adenine: Adenine (A) is one of four chemical mimic aspects of a disease found in humans.
bases in DNA; the other three are cytosine (C), Animal models are used to obtain information
guanine (G), and thymine (T). Within the DNA about a disease and its prevention, diagnosis,
molecule, adenine bases located on one strand and treatment. By using animals, researchers can
form chemical bonds with thymine bases on the carry out experiments that would be impractical
opposite strand. The sequence of four DNA bases or ethically prohibited with humans.
encodes the cell’s genetic instructions. A form
of adenine called adenosine triphosphate (ATP) antibody: An antibody is a protein component
serves as an energy storage molecule and is used of the immune system that circulates in the
to power many chemical reactions within the cell. blood and recognizes and neutralizes foreign
substances such as bacteria and viruses. After
allele: An allele is one of two or more versions exposure to a foreign substance, called an
of a gene. An individual inherits two alleles antigen, antibodies continue to circulate in
for each gene, one from each parent. If the the blood, providing protection against future
two alleles are the same, the individual is exposures to that antigen.
39
Human Genetic Variation
40
base pair: A base pair is two chemical bases A cancerous tumor can spread to other parts of
bonded to one another forming a “rung of the the body and, if left untreated, be fatal.
DNA ladder.” The DNA molecule consists of
two strands that wind around each other like a candidate gene: A candidate gene is a gene
twisted ladder. Each strand has a backbone made whose chromosomal location is associated with a
of alternating sugar (deoxyribose) and phosphate particular disease or other phenotype. Because of
groups. Attached to each sugar is one of four its location, the gene is suspected of causing the
bases—adenine (A), cytosine (C), guanine (G), or disease or other phenotype.
thymine (T). The two strands are held together by
hydrogen bonds between the bases, with adenine carcinogen: A carcinogen is an agent with the
forming a base pair with thymine, and cytosine capacity to cause cancer in humans. Carcinogens
forming a base pair with guanine. may be natural, such as aflatoxin, which is
produced by a fungus and sometimes found on
bioinformatics: Bioinformatics is a subdiscipline stored grains, or manmade, such as asbestos or
of biology and computer science concerned with tobacco smoke. Carcinogens work by interacting
the acquisition, storage, analysis, and dissemination with a cell’s DNA and inducing genetic mutations.
of biological data, most often DNA and amino
acid sequences. Bioinformatics uses computer carrier: A carrier is an individual who carries
programs for a variety of applications, including and is capable of passing on a genetic mutation
determining gene and protein functions, establishing associated with a disease and may or may not
evolutionary relationships, and predicting the display disease symptoms. Carriers are associated
three-dimensional shapes of proteins. with diseases inherited as recessive traits. In
order to have the disease, an individual must
birth defect: A birth defect is an abnormality have inherited mutated alleles from both parents.
present at birth. Also called a congenital defect, An individual having one normal allele and one
it can be caused by a genetic mutation, an mutated allele does not have the disease. Two
unfavorable environment during pregnancy, or a carriers may produce children with the disease.
combination of both. The effect of a birth defect
can be mild, severe, or incompatible with life. carrier screening: Carrier screening is a type of
genetic testing performed on people who display
BRCA1/BRCA2: BRCA1 and BRCA2 are the first no symptoms for a genetic disorder but may be at
two genes found to be associated with inherited risk for passing it on to their children. A carrier
forms of breast cancer. Both genes normally act for a genetic disorder has inherited one normal
as tumor suppressors, meaning that they help and one abnormal allele for a gene associated with
regulate cell division. When these genes are the disorder. A child must inherit two abnormal
rendered inactive due to mutation, uncontrolled alleles for symptoms to appear. Prospective
cell growth results, leading to breast cancer. parents with a family history of a genetic disorder
Women with mutations in either gene have a are candidates for carrier screening.
much higher risk of developing breast cancer
than women without mutations in the genes. cell: A cell is the basic building block of living
things. All cells can be sorted into one of two
cancer: Cancer is a group of diseases characterized groups: eukaryotes and prokaryotes. A eukaryote
by uncontrolled cell growth. Cancer begins when has a nucleus and membrane-bound organelles,
a single cell mutates, resulting in a breakdown while a prokaryote does not. Plants and animals
of the normal regulatory controls that keep are made of numerous eukaryotic cells, while
cell division in check. These mutations can be many microbes, such as bacteria, consist of single
inherited, caused by errors in DNA replication, cells. An adult human body is estimated to contain
or result from exposure to harmful chemicals. between 10 and 100 trillion cells.
41
Glossary
Human Genetic Variation
cell cycle: A cell cycle is a series of events that centrosome: A centrosome is a cellular structure
takes place in a cell as it grows and divides. A involved in the process of cell division. Before
cell spends most of its time in what is called cell division, the centrosome duplicates and
interphase, and during this time, it grows, then, as division begins, the two centrosomes
replicates its chromosomes, and prepares for move to opposite ends of the cell. Proteins called
cell division. The cell then leaves interphase, microtubules assemble into a spindle between the
undergoes mitosis, and completes its division. two centrosomes and help separate the replicated
The resulting cells, known as daughter cells, chromosomes into the daughter cells.
each enter their own interphase and begin a
new round of the cell cycle. chromatid: A chromatid is one of two identical
halves of a replicated chromosome. During cell
cell membrane (plasma membrane): The cell division, the chromosomes first replicate so that
membrane, also called the plasma membrane, each daughter cell receives a complete set of
is found in all cells and separates the interior chromosomes. Following DNA replication, the
of the cell from the outside environment. The chromosome consists of two identical structures
cell membrane consists of a lipid bilayer that is called sister chromatids, which are joined at
semipermeable. The cell membrane regulates the centromere.
the transport of materials entering and exiting
the cell. chromatin: Chromatin is a substance within
a chromosome consisting of DNA and protein.
centimorgan: A centimorgan is a unit used The DNA carries the cell’s genetic instructions.
to measure genetic linkage. One centimorgan The major proteins in chromatin are histones,
equals a 1 percent chance that a marker on which help package the DNA in a compact form
a chromosome will become separated from a that fits inside the cell nucleus. Changes in
second marker on the same chromosome due to chromatin structure are associated with DNA
crossing over in a single generation. It translates replication and gene expression.
to approximately 1 million base pairs of DNA
sequence in the human genome. The centimorgan chromosome: A chromosome is an organized
is named after the American geneticist Thomas package of DNA found in the nucleus of the cell.
Hunt Morgan. Different organisms have different numbers
of chromosomes. Humans have 23 pairs
centriole: Centrioles are paired barrel-shaped of chromosomes—22 pairs of numbered
organelles located in the cytoplasm of animal chromosomes, called autosomes, and one pair
cells near the nuclear envelope. Centrioles play of sex chromosomes, X and Y. Each parent
a role in organizing microtubules that serve as contributes one chromosome to each pair so
the cell’s skeletal system. They help determine that offspring get half of their chromosomes
the locations of the nucleus and other organelles from their mother and half from their father.
within the cell.
cloning: Cloning is the process of making
centromere: A centromere is a constricted region identical copies of an organism, cell, or DNA
of a chromosome that separates it into a short arm sequence. Molecular cloning is a process by
(p) and a long arm (q). During cell division, the which scientists amplify a desired DNA sequence.
chromosomes first replicate so that each daughter The target sequence is isolated, inserted into
cell receives a complete set of chromosomes. another DNA molecule (known as a vector), and
Following DNA replication, the chromosome introduced into a suitable host cell. Then, each
consists of two identical structures called sister time the host cell divides, it replicates the foreign
chromatids, which are joined at the centromere. DNA sequence along with its own DNA. Cloning
can also refer to asexual reproduction.
42
codominance: Codominance is a relationship crossing over: Crossing over is the swapping
between two versions of a gene. Individuals of genetic material that occurs in the germ line.
receive one version of a gene, called an allele, During the formation of egg and sperm cells, also
from each parent. If the alleles are different, the known as meiosis, paired chromosomes from each
dominant allele will usually be expressed, while parent align so that similar DNA sequences from
the effect of the other allele, called recessive, is the paired chromosomes cross over one another.
masked. In codominance, however, neither allele Crossing over results in a shuffling of genetic
is recessive, and the phenotypes of both alleles material and is an important cause of the genetic
are expressed. variation seen among offspring.
codon: A codon is a trinucleotide sequence of DNA cystic fibrosis: Cystic fibrosis is a hereditary
or RNA that corresponds to a specific amino acid. disease characterized by faulty digestion,
The genetic code describes the relationship between breathing problems, respiratory infections from
the sequence of DNA bases (A, C, G, and T) in a mucus buildup, and the loss of salt in sweat. The
gene and the corresponding protein sequence that disease is caused by mutations in a single gene
it encodes. The cell reads the sequence of the gene and is inherited as an autosomal recessive trait,
in groups of three bases. There are 64 different meaning that an affected individual inherits two
codons: 61 specify amino acids, while the remaining mutated copies of the gene. In the past, cystic
three are used as stop signals. fibrosis was almost always fatal in childhood.
Today, however, patients commonly live to be
complex disease: A complex disease is caused 30 years or older.
by the interaction of multiple genes and
environmental factors. Complex diseases are cytogeneticist: A cytogeneticist is a geneticist
also called multifactorial. Examples of complex who specializes in the study of chromosomes
diseases include cancer and heart disease. and the structure and function of the cell.
43
Glossary
Human Genetic Variation
deletion: Deletion is a type of mutation involving sample from a suspect. If the two DNA profiles
the loss of genetic material. It can be small, are a match, then the evidence came from that
involving a single missing DNA base pair, or suspect. Conversely, if the two DNA profiles
large, involving a piece of a chromosome. do not match, then the evidence cannot have
come from the suspect. DNA fingerprinting
diabetes (diabetes mellitus): Diabetes mellitus is also used to establish paternity.
is a disease characterized by an inability to make
or use the hormone insulin. Insulin is needed DNA replication: DNA replication is the process
by cells to metabolize glucose, the body’s main by which a molecule of DNA is duplicated. When
source of chemical energy. Type I diabetes, also a cell divides, it must first duplicate its genome
called insulin-dependent diabetes mellitus, is so that each daughter cell winds up with a
usually caused by an autoimmune destruction complete set of chromosomes.
of insulin-producing cells. Type II diabetes, also
called non-insulin-dependent diabetes mellitus, DNA sequencing: DNA sequencing is a laboratory
occurs when cells become resistant to the effects technique used to determine the exact sequence
of insulin. of bases (A, C, G, and T) in a DNA molecule. The
DNA base sequence carries the information a cell
diploid: Diploid is a cell or organism that has needs to assemble protein and RNA molecules.
paired chromosomes, one from each parent. In DNA sequence information is important to
humans, cells other than human sex cells are scientists investigating the functions of genes.
diploid and have 23 pairs of chromosomes. Human The technology of DNA sequencing was made
sex cells (egg and sperm cells) contain a single faster and less expensive as a part of the Human
set of chromosomes and are known as haploid. Genome Project.
DNA (deoxyribonucleic acid): DNA is the dominant: Dominant refers to the relationship
chemical name for the molecule that carries between two versions of a gene. Individuals
genetic instructions in all living things. The receive two versions of each gene, known as
DNA molecule consists of two strands that wind alleles, from each parent. If the alleles of a gene
around one another to form a shape known are different, one allele will be expressed; it is
as a double helix. Each strand has a backbone the dominant gene. The effect of the other allele,
made of alternating sugar (deoxyribose) and called recessive, is masked.
phosphate groups. Attached to each sugar is one
of four bases—adenine (A), cytosine (C), guanine double helix: Double helix is the description
(G), and thymine (T). The two strands are held of the structure of a DNA molecule. A DNA
together by bonds between the bases; adenine molecule consists of two strands that wind
bonds with thymine, and cytosine bonds with around each other like a twisted ladder. Each
guanine. The sequence of the bases along the strand has a backbone made of alternating
backbones serves as instructions for assembling groups of sugar (deoxyribose) and phosphate
protein and RNA molecules. groups. Attached to each sugar is one of four
bases: adenine (A), cytosine (C), guanine (G),
DNA fingerprinting: DNA fingerprinting is a or thymine (T). The two strands are held
laboratory technique used to establish a link together by bonds between the bases, with
between biological evidence and a suspect in adenine forming a base pair with thymine and
a criminal investigation. A DNA sample taken cytosine forming a base pair with guanine.
from a crime scene is compared with a DNA
44
Down syndrome (trisomy 21): Down syndrome appearance. Smooth endoplasmic reticulum lacks
is a genetic disease resulting from a chromosomal ribosomes and helps synthesize and concentrate
abnormality. An individual with Down syndrome various substances that the cell needs.
inherits all or part of an extra copy of chromosome
21. Symptoms associated with the syndrome enzyme: An enzyme is a biological catalyst and
include mental retardation, distinctive facial is almost always a protein. It speeds up the rate
characteristics, and increased risk for heart of a specific chemical reaction in the cell. The
defects and digestive problems, which can range enzyme is not destroyed during the reaction and
from mild to severe. The risk of having a child is used over and over. A cell contains thousands
with Down syndrome rises with the mother’s of different types of enzyme molecules, each
age at the time of conception. specific to a particular chemical reaction.
45
Glossary
Human Genetic Variation
exon: An exon is the portion of a gene that on the X chromosome. Since males have a single
codes for amino acids. In the cells of plants and copy of the X chromosome, they show symptoms
animals, most gene sequences are broken up by if that gene on their X chromosome is mutated.
one or more DNA sequences called introns. The Females have a second, usually normal, copy
parts of the gene sequence that are expressed of the gene on their other X chromosome.
in the protein are called exons because they are Consequently, they are less likely to show
expressed, while the parts of the gene sequence symptoms of the syndrome.
that are not expressed in the protein are called
introns because they come in between—or frameshift mutation: A frameshift mutation
interfere with—the exons. is a type of mutation involving the insertion or
deletion of a nucleotide in which the number
family history: A family history is a record of of deleted base pairs is not divisible by three.
medical information about an individual and that “Divisible by three” is important because the
individual’s biological family. Human genetic cell reads a gene in groups of three bases. Each
data are becoming more prevalent and easy to group of three bases corresponds to 1 of 20
obtain. Increasingly, these data are being used to different amino acids used to build a protein.
identify individuals who are at increased risk for If a mutation disrupts this reading frame, then
developing genetic disorders that run in families. the entire DNA sequence following the mutation
will be read incorrectly.
first-degree relative: A first-degree relative is
a family member who shares about 50 percent fraternal twins: Fraternal twins are also called
of their genes with a particular individual in a dizygotic twins. They result from the fertilization
family. First-degree relatives include parents, of two separate eggs during the same pregnancy.
offspring, and siblings. Fraternal twins may be of the same or different
sexes. They share half their genes, just like any
fluorescence in situ hybridization (FISH): other siblings. In contrast, twins that result from
Fluorescence in situ hybridization (FISH) is a the fertilization of a single egg that then splits in
laboratory technique for detecting and locating two are called monozygotic, or identical, twins.
a specific DNA sequence on a chromosome. The Identical twins share all their genes and are
technique relies on exposing chromosomes to always the same sex.
a small DNA sequence called a probe that has a
fluorescent molecule attached to it. The probe gene: The gene is the basic physical unit of
sequence binds to its corresponding sequence inheritance. Genes are passed from parents to
on the chromosome. offspring and contain the information needed
to specify traits. Genes are arranged, one after
founder effect: The founder effect is the reduction another, on structures called chromosomes.
in genetic variation that results when a small A chromosome contains a single, long DNA
subset of a large population establishes a new molecule, only a portion of which corresponds to
colony. The new population may be very different a single gene. Humans have about 23,000 genes
from the original population, both in terms of its on their chromosomes.
genotypes and phenotypes. In some cases, the
founder effect plays a role in the emergence of gene amplification: Gene amplification is
new species. an increase in the number of copies of a gene
sequence. Cancer cells sometimes produce
fragile X syndrome: Fragile X syndrome is multiple copies of genes in response to signals
a hereditary disorder mostly affecting males. from other cells or their environment. The term
Symptoms include mental retardation, distinctive can also refer to polymerase chain reaction (PCR),
facial features, and poor muscle tone. The a laboratory technique scientists use to amplify
syndrome is caused by mutations in a gene gene sequences in a test tube.
46
gene-environment interaction: Gene- gene therapy: Gene therapy is an experimental
environment interaction is an influence on the technique for treating disease by altering the
expression of a trait that results from the interplay patient’s genetic material. Most often, gene therapy
between genes and the environment. Some traits works by introducing a healthy copy of a defective
are strongly influenced by genes, while others gene into the patient’s cells.
are strongly influenced by the environment.
Most traits, however, are influenced by one genetic code: The genetic code is the instructions
or more genes interacting in complex ways in a gene that tell the cell how to make a specific
with the environment. protein. A, C, G, and T are the “letters” of the
DNA code; they stand for the chemicals adenine
gene expression: Gene expression is the process (A), cytosine (C), guanine (G), and thymine (T),
by which the information encoded in a gene is respectively, that make up the nucleotide bases
used to direct the assembly of a protein molecule. of DNA. Each gene’s code combines the four
The cell reads the sequence of the gene in groups chemicals in various ways to spell out three-letter
of three bases. Each group of three bases (codon) “words” that specify which amino acid is needed
corresponds to 1 of 20 different amino acids used at every step in making a protein.
to build the protein.
genetic counseling: Genetic counseling is the
gene mapping: Gene mapping is the process professional interaction between a healthcare
of establishing the locations of genes on the provider with specialized knowledge of genetics
chromosomes. Early gene maps used linkage and an individual or family. The genetic counselor
analysis. The closer two genes are to each other determines whether a condition in the family may
on the chromosome, the more likely it is that be genetic and estimates the chances that another
they will be inherited together. By following relative may be affected. Genetic counselors also
inheritance patterns, the relative positions of offer and interpret genetic tests that may help to
genes can be determined. More recently, scientists estimate risk of disease. The genetic counselor
have used recombinant DNA (rDNA) techniques conveys information in an effort to address
to establish the actual physical locations of genes concerns of the client and provides psychological
on the chromosomes. counseling to help families adapt to their
condition or risk.
gene pool: A gene pool is the total genetic
diversity found within a population or a species. genetic discrimination: Genetic discrimination
A large gene pool has extensive genetic diversity is prejudice directed against people who have or
and is better able to withstand the challenges may have a genetic disease. Genetic discrimination
posed by environmental stresses. Inbreeding can involve being denied employment or health
contributes to the creation of a small gene pool insurance. In a healthcare context, it can refer to
and makes populations or species more likely to people being treated based on their genetic status
go extinct when faced with some type of stress. rather than by some more relevant criterion.
gene regulation: Gene regulation is the process genetic drift: Genetic drift is a mechanism of
of turning genes on and off. During early evolution. It refers to random fluctuations in
development, cells begin to take on specific the frequencies of alleles from generation to
functions. Gene regulation ensures that the generation due to chance events. Genetic drift
appropriate genes are expressed at the proper can cause traits to be dominant or to disappear
times. Gene regulation can also help an organism from a population. The effects of genetic drift
respond to its environment. Gene regulation are most pronounced in small populations.
is accomplished by a variety of mechanisms
including chemically modifying genes and using
regulatory proteins to turn genes on or off.
47
Glossary
Human Genetic Variation
48
genetic variation: Genetic variation refers to Golgi body: A Golgi body, also known as a
diversity in gene frequencies. Genetic variation Golgi apparatus, is a cell organelle that helps
can refer to differences between individuals or process and package proteins and lipid molecules,
to differences between populations. Mutation especially proteins destined to be exported from
is the ultimate source of genetic variation, but the cell. Named after its discoverer, Camillo
mechanisms such as sexual reproduction and Golgi, the Golgi body appears as a series of
genetic drift contribute to it as well. stacked membranes.
genome: The genome is the entire set of genetic guanine: Guanine (G) is one of four chemical
instructions in a cell. In humans, the genome bases in DNA, with the other three being adenine
consists of 23 pairs of chromosomes, found in (A), cytosine (C), and thymine (T). Within the
the nucleus, as well as a small chromosome found DNA molecule, guanine bases located on one
in the cell’s mitochondria. These chromosomes, strand form chemical bonds with cytosine bases
taken together, contain approximately 3.1 billion on the opposite strand. The sequence of four DNA
bases of DNA sequence. bases encodes the cell’s genetic instructions.
49
Glossary
Human Genetic Variation
50
inherited: An inherited trait is one that is LOD score: LOD stands for “logarithm of the
genetically determined. Inherited traits are passed odds.” In genetics, the LOD score is a statistical
from parent to offspring according to the rules estimate of whether two genes, or a gene and a
of Mendelian genetics. Most traits are not strictly disease gene, are likely to be located near each
determined by genes, but rather are influenced by other on a chromosome and are therefore likely
both genes and environment. to be inherited together. A LOD score of 3 or
higher is generally understood to mean that
insertion: Insertion is a type of mutation two genes are located close to each other. In
involving the addition of genetic material. terms of significance, a LOD score of 3 means
An insertion mutation can be small, involving a the odds are 1,000 to 1 that the two genes are
single extra DNA base pair, or large, involving a linked and, therefore, inherited together.
piece of a chromosome.
lymphocyte: A lymphocyte is a type of white
intron: An intron is a portion of a gene that does blood cell that is part of the immune system.
not code for amino acids. In the cells of plants There are two main types of lymphocytes: B cells
and animals, most gene sequences are broken and T cells. The B cells produce antibodies that
up by one or more introns. The parts of the gene attack invading bacteria, viruses, and toxins.
sequence that are expressed in the protein are The T cells destroy the body’s own cells that
called exons because they are expressed, while have themselves been taken over by viruses
the parts of the gene sequence that are not or become cancerous.
expressed in the protein are called introns
because they come in between the exons. lyonization: Lyonization is commonly known
as X-inactivation. In mammals, males receive
karyotype: A karyotype is an individual’s one copy of the X chromosome while females
collection of chromosomes. The term also refers receive two copies. To prevent female cells from
to a laboratory technique that produces an image having twice as many gene products from the
of an individual’s chromosomes. The karyotype is X chromosomes as males, one copy of the X
used to look for abnormal numbers or structures chromosome in each female cell is inactivated.
of chromosomes. In placental mammals, the choice of which X
chromosome is inactivated is random, whereas
knockout: A knockout typically refers to an in marsupials, it is always the paternal copy
organism that has been genetically engineered that is inactivated.
to lack one or more specific genes. Scientists
create knockouts (often in mice) so that they lysosome: A lysosome is a membrane-bound
can study the impact of the missing genes and cell organelle that contains digestive enzymes.
learn something about the genes’ function. Lysosomes are involved with various cell
processes. They break down excess or worn-
linkage: Linkage is the close association of out cell parts. They may be used to destroy
genes or other DNA sequences on the same invading viruses and bacteria. If the cell is
chromosome. The closer two genes are to each damaged beyond repair, lysosomes can help it
other on the chromosome, the greater the self-destruct in a process called programmed
probability that they will be inherited together. cell death, or apoptosis.
51
Glossary
Human Genetic Variation
mapping: Mapping is the process of making a Mendel performed thousands of crosses with
representative diagram cataloging the genes and garden peas at his monastery during the middle of
other features of a chromosome and showing the 19th century. Mendel explained his results by
their relative locations. Cytogenetic maps are describing two laws of inheritance that introduced
made using photomicrographs of chromosomes the idea of dominant and recessive genes.
stained to reveal structural variations. Genetic
maps use the idea of linkage to estimate the messenger RNA (mRNA): Messenger RNA
relative locations of genes. Physical maps, made (mRNA) is a single-stranded RNA molecule that
using recombinant DNA (rDNA) technology, is complementary to one of the DNA strands
show the actual physical locations of landmarks of a gene. The mRNA is an RNA version of the
along a chromosome. gene that leaves the cell nucleus and moves to
the cytoplasm where proteins are made. During
marker: A marker is a DNA sequence with a protein synthesis, an organelle called a ribosome
known physical location on a chromosome. moves along the mRNA, reads its base sequence,
Markers can help link an inherited disease and uses the genetic code to translate each three-
with the responsible genes. DNA segments base triplet, or codon, into its corresponding
close to each other on a chromosome tend amino acid.
to be inherited together. Markers are used to
track the inheritance of a nearby gene that has metagenomics: Metagenomics is the study of a
not yet been identified but whose approximate collection of genetic material (genomes) from a
location is known. The marker itself may be a mixed community of organisms. Metagenomics
part of a gene or may have no known function. usually refers to the study of microbial communities.
meiosis: Meiosis is the formation of egg and metaphase: Metaphase is a stage during the
sperm cells. In sexually reproducing organisms, process of cell division (mitosis or meiosis).
body cells are diploid, meaning they contain two Usually, individual chromosomes cannot
sets of chromosomes (one set from each parent). be observed in the cell nucleus. However,
To maintain this state, the egg and sperm that during metaphase of mitosis or meiosis,
unite during fertilization are haploid, meaning the chromosomes condense and become
they each contain a single set of chromosomes. distinguishable as they align in the center of the
During meiosis, diploid cells undergo DNA dividing cell. Metaphase chromosomes are used
replication followed by two rounds of cell during the karyotyping procedure used to look
division, producing four haploid sex cells. for chromosomal abnormalities.
Mendel, Johann (Gregor): Gregor Mendel was an microarray technology: Microarray technology
Austrian monk who in the 19th century worked is a developing technology used to study the
out the basic laws of inheritance, even before the expression of many genes at once. It involves
term “gene” had been coined. In his monastery placing thousands of gene sequences in known
garden, Mendel performed thousands of crosses locations on a glass slide called a gene chip. A
with garden peas. Mendel explained his results by sample containing DNA or RNA is placed in
describing two laws of inheritance that introduced contact with the gene chip. Complementary
the idea of dominant and recessive traits. base pairing between the sample and the gene
sequences on the chip produces light that is
Mendelian inheritance: Mendelian inheritance measured. Areas on the chip producing light
refers to patterns of inheritance of organisms that identify genes expressed in the sample.
reproduce sexually. The Austrian monk Gregor
52
microbiome: A microbiome is all of the genetic Monosomy can be partial if a portion of the
material found within an individual microbe such second chromosome copy is present. Monosomy,
as a bacterium, fungal cell, or virus. It also may or partial monosomy, is the cause of some human
refer to the collection of genetic material found diseases such as Turner syndrome and Cri du
in a community of microbes that live together. Chat syndrome.
53
Glossary
Human Genetic Variation
noncoding DNA: Noncoding DNA sequences nucleic acid: Nucleic acids are an important class
do not code for amino acids. Most noncoding of macromolecules found in all cells and viruses.
DNA lies between genes on the chromosome The functions of nucleic acids have to do with the
and has no known function. Other noncoding storage and expression of genetic information.
DNA, called introns, is found within genes. Deoxyribonucleic acid (DNA) encodes the
Some noncoding DNA plays a role in the information the cell needs to make proteins. A
regulation of gene expression. related type of nucleic acid, called ribonucleic
acid (RNA), comes in different molecular forms
nondirectiveness: Nondirectiveness refers to that participate in protein synthesis.
the nature of the genetic counseling process.
According to the principle of nondirectiveness, nucleolus: The nucleolus is a region found
the genetic counselor has the responsibility to within the cell nucleus concerned with producing
provide the client with accurate information and assembling the cell’s ribosomes. Following
about a test or outcome but should remain assembly, ribosomes are transported to the cell
neutral and not try to influence the decisions cytoplasm, where they serve as the sites for
made by the client. protein synthesis.
54
nucleus: A nucleus is a membrane-bound peptide: A peptide is one or more amino acids
organelle that contains the cell’s chromosomes. linked by chemical bonds. The term also refers
Pores in the nuclear membrane allow molecules to the type of chemical bond that joins the amino
to pass into and out of the nucleus. acids together. A series of linked amino acids is
a polypeptide. The cell’s proteins are made from
oncogene: An oncogene is a mutated gene that one or more polypeptides.
contributes to the development of a cancer. In
their normal, unmutated state, oncogenes are personalized medicine: Personalized medicine
called proto-oncogenes, and they play roles in the is an emerging practice of medicine that uses
regulation of cell division. Some oncogenes work an individual’s genetic profile to guide decisions
like putting your foot down on the accelerator of about the prevention, diagnosis, and treatment
a car, pushing a cell to divide. Other oncogenes of disease. Knowledge of a patient’s genetic profile
work like removing your foot from the brake while can help doctors select the proper medication or
parked on a hill, also causing the cell to divide. therapy and administer it using the proper dose or
regimen. Personalized medicine is being advanced
open reading frame: An open reading frame is a through data from the Human Genome Project.
portion of a DNA molecule that, when translated
into amino acids, contains no stop codons. The pharmacogenomics: Pharmacogenomics is a
genetic code reads DNA sequences in groups of branch of pharmacology concerned with using
three base pairs, which means that a double- DNA and amino acid sequence data to inform
stranded DNA molecule can read in any of six drug development and testing. An important
possible reading frames—three in the forward application of pharmacogenomics is correlating
direction and three in the reverse. A long open individual genetic variation with drug responses.
reading frame is likely part of a gene.
phenotype: A phenotype is an individual’s
organ: In biology, an organ (from the Latin observable traits, such as height, eye color, and
“organum,” meaning an instrument or tool) is blood type. The genetic contribution to the
a collection of tissues that structurally form a phenotype is called the genotype. Some traits are
functional unit specialized to perform a particular largely determined by the genotype, while others
function. Your heart, kidneys, and lungs are are largely determined by environmental factors.
examples of organs.
phosphate backbone: A phosphate backbone is
organelle: An organelle is a subcellular structure the portion of the DNA double helix that provides
that has one or more specific jobs to perform in structural support to the molecule. DNA consists
the cell, much like an organ does in the body. of two strands that wind around each other like a
Among the more important cell organelles are twisted ladder. Each strand has a backbone made
the nuclei, which store genetic information; of alternating sugar (deoxyribose) and phosphate
mitochondria, which produce chemical energy; groups. Attached to each sugar is one of four
and ribosomes, which assemble proteins. bases—adenine (A), cytosine (C), guanine (G), or
thymine (T). The two strands are held together by
pedigree: A pedigree is a genetic representation bonds between the bases, with adenine forming
of a family tree that diagrams the inheritance of a base pair with thymine and cytosine forming a
a trait or disease though several generations. The base pair with guanine.
pedigree shows the relationships between family
members and indicates which individuals express
or silently carry the trait in question.
55
Glossary
Human Genetic Variation
physical map: A physical map of a chromosome polygenic trait: A polygenic trait is one whose
or a genome shows the physical locations of genes phenotype is influenced by more than one gene.
and other DNA sequences of interest. Physical Traits that display a continuous distribution,
maps are used to help scientists identify and such as height or skin color, are polygenic.
isolate genes by positional cloning. The inheritance of polygenic traits does not
show the phenotypic ratios characteristic of
plasma membrane (cell membrane): The plasma Mendelian inheritance, though each of the
membrane, also called the cell membrane, is the genes contributing to the trait is inherited as
membrane found in all cells that separates the described by Gregor Mendel. Many polygenic
interior of the cell from the outside environment. traits are also influenced by the environment
In bacterial and plant cells, a cell wall is attached and are called multifactorial.
to the plasma membrane on its outside surface.
The plasma membrane consists of a lipid bilayer polymerase chain reaction (PCR): Polymerase
that is semipermeable. The plasma membrane chain reaction (PCR) is a laboratory technique
regulates the transport of materials entering and used to amplify DNA sequences. The method
exiting the cell. involves using short DNA sequences called
primers to select the portion of the genome to
plasmid: A plasmid is a small, often circular be amplified. The temperature of the sample is
DNA molecule found in bacteria and other repeatedly raised and lowered to help a DNA
cells. Plasmids are separate from the bacterial replication enzyme copy the target DNA sequence.
chromosome and replicate independently of it. The technique can produce a billion copies of the
They generally carry only a small number of target sequence in just a few hours.
genes, notably some associated with antibiotic
resistance. Plasmids may be passed between polymorphism: Polymorphism involves
different bacterial cells. one of two or more variants of a particular
DNA sequence. The most common type of
point mutation: A point mutation is when a single polymorphism involves variation at a single
base pair is altered. Point mutations can have base pair. Polymorphisms can also be much
one of three effects. First, the base substitution larger and involve long stretches of DNA.
can be a silent mutation, where the altered codon Scientists are studying how single nucleotide
corresponds to the same amino acid. Second, the polymorphisms, or SNPs (pronounced “snips”),
base substitution can be a missense mutation, in the human genome correlate with disease,
where the altered codon corresponds to a different drug response, and other phenotypes.
amino acid. Or third, the base substitution can
be a nonsense mutation, where the altered codon population genomics: Population genomics
corresponds to a stop signal. is the application of genomic technologies
to understand populations of organisms. In
polydactyly: Polydactyly is an abnormality humans, population genomics typically refers
characterized by extra fingers or toes. The to applying technology in the quest to
condition may be present as part of a collection understand how genes contribute to our
of abnormalities, or it may exist by itself. health and well-being.
When by itself, it is inherited as an autosomal
dominant trait.
56
positional cloning: Positional cloning is a promoter: A promoter is a sequence of DNA
laboratory technique used to locate the position of needed to turn a gene on or off. The process of
a disease-associated gene along the chromosome. transcription is initiated at the promoter. Usually
This approach works even when little or no found near the beginning of a gene, the promoter
information is available about the biochemical has a binding site for the enzyme used to make a
basis of the disease. Positional cloning is used in messenger RNA (mRNA) molecule.
conjunction with linkage analysis. It involves the
isolation of partially overlapping DNA segments prostate cancer: Prostate cancer is a disease
that progress along the chromosome toward a characterized by uncontrolled cell growth in
candidate gene. the prostate gland, which is part of the male
reproductive system. Prostate cancer generally
primer: A primer is a short, single-stranded affects men over the age of 50. It is responsible
DNA sequence used in the polymerase chain for more deaths among men than any other
reaction (PCR) technique. In the PCR method, cancer except lung cancer.
a pair of primers is used to hybridize with the
sample DNA and define the region of the DNA protein: Proteins are an important class of
that will be amplified. Primers are also referred molecules found in all living cells. A protein is
to as oligonucleotides. composed of one or more long chains of amino
acids, the sequence of which corresponds to
proband: A proband is an individual being the DNA sequence of the gene that encodes
studied or reported on. A proband is usually it. Proteins play a variety of roles in the cell,
the first affected individual in a family who including structural (cytoskeleton), mechanical
brings a genetic disorder to the attention of (muscle), biochemical (enzymes), and cell
the medical community. signaling (hormones). Proteins are also an
essential part of diet.
probe: A probe is a single-stranded sequence of
DNA or RNA used to search for its complementary pseudogene: A pseudogene is a DNA sequence
sequence in a sample genome. The probe is placed that resembles a gene but has been mutated into
into contact with the sample under conditions an inactive form over the course of evolution. A
that allow the probe to hybridize with its pseudogene shares an evolutionary history with
complementary sequence. The probe is labeled a functional gene and can provide insight into
with a radioactive or chemical tag that allows their shared ancestry.
its binding to be visualized. In a similar way,
labeled antibodies are used to probe a sample race: Race is a fluid concept used to group people
for the presence of a specific protein. according to various factors, including ancestral
background and social identity. Race is also
progeria: Progeria is a rare disease characterized used to group people that share a set of visible
by accelerated aging. The classic form of progeria characteristics, such as skin color and facial
is called Hutchinson-Gilford progeria syndrome features. Though these visible traits are influenced
(HGPS), named for the doctors who first described by genes, the vast majority of genetic variation
it. Progeria is caused by a mutation in the gene exists within racial groups and not between
for LMNA (pronounced “Lamin A”). The LMNA them. Race is an ideology, and for this reason,
protein provides structural support to the cell many scientists believe that race should be more
nucleus. When the gene is mutated, the LMNA accurately described as a social construct and
protein produces nuclear instability that leads not a biological one.
to premature aging. Affected persons commonly
die from heart disease during late childhood.
57
Glossary
Human Genetic Variation
recessive: Recessive is a quality found in the A variety of different retroviruses causes human
relationship between two versions of a gene. diseases such as AIDS and some forms of cancer.
Individuals receive one version of a gene, called
an allele, from each parent. If the alleles are ribosome: A ribosome is a cellular particle
different, the dominant allele will be expressed, made of RNA and protein that serves as the site
while the effect of the other allele, called for protein synthesis in the cell. The ribosome
recessive, is masked. In the case of a recessive reads the sequence of the messenger RNA
genetic disorder, an individual must inherit (mRNA) and, using the genetic code, translates
two copies of the mutated allele for the disease the sequence of RNA bases into a sequence of
to be present. amino acids.
recombinant DNA (rDNA): Recombinant DNA risk: Risk, in the context of genetics, refers
(rDNA) is a technology that uses enzymes to cut to the probability that an individual will be
and paste together DNA sequences of interest. affected by a particular genetic disorder. Genes
The recombined DNA sequences can be placed and environment both influence risk. Some
into vehicles called vectors that ferry the DNA individuals’ risk may be higher because they
into a suitable host cell where it can be copied inherit genes that cause or increase susceptibility
or expressed. to a disorder. Other individuals may be at
higher risk because they live or work in an
repressor: A repressor is a protein that turns environment that promotes the development
off the expression of one or more genes. The of the disorder.
repressor protein works by binding to the gene’s
promoter region, preventing the production of RNA (ribonucleic acid): Ribonucleic acid
messenger RNA (mRNA). (RNA) is a molecule similar to DNA. Unlike
DNA, RNA is single-stranded. An RNA strand
restriction enzyme: A restriction enzyme is an has a backbone made of alternating sugar (ribose)
enzyme isolated from bacteria that cuts DNA and phosphate groups. Attached to each sugar
molecules at specific sequences. The isolation of is one of four bases—adenine (A), uracil (U),
these enzymes was critical to the development cytosine (C), or guanine (G). Different types
of recombinant DNA (rDNA) technology and of RNA exist in the cell: messenger RNA (mRNA),
genetic engineering. ribosomal RNA (rRNA), and transfer RNA
(tRNA). More recently, some small RNAs
restriction fragment length polymorphism have been found to be involved in regulating
(RFLP): Restriction fragment length polymorphism gene expression.
(RFLP) is a type of polymorphism that results
from variation in the DNA sequence recognized sex chromosome: A sex chromosome is a
by restriction enzymes. These are bacterial type of chromosome that participates in sex
enzymes that scientists use to cut DNA molecules determination. Humans and most other
at known locations. RFLPs (pronounced “rif lips”) mammals have two sex chromosomes, the X
are used as markers on genetic maps. Typically, and the Y. Females have two X chromosomes
gel electrophoresis is used to visualize RFLPs. in their cells, while males have both an X and
a Y chromosome in their cells. Egg cells all
retrovirus: A retrovirus is a virus that uses contain an X chromosome, while sperm cells
RNA as its genetic material. When a retrovirus contain an X or a Y chromosome. This means
infects a cell, it makes a DNA copy of its genome that during fertilization, the male determines
that is inserted into the DNA of the host cell. the sex of the offspring.
58
sex-linked: Sex-linked is a trait in which a gene Southern blot: Southern blotting is a laboratory
is located on a sex chromosome. In humans, technique used to detect a specific DNA sequence
the term generally refers to traits influenced by in a blood or tissue sample. A restriction enzyme
genes on the X chromosome. This is because is used to cut a sample of DNA into fragments that
the X chromosome is large and contains many are separated using gel electrophoresis. The DNA
more genes than the smaller Y chromosome. fragments are transferred out of the gel to the
In a sex-linked disease, it is usually males who surface of a membrane. The membrane is exposed
are affected because they have a single copy of to a DNA probe labeled with a radioactive or
the X chromosome that carries the mutation. chemical tag. If the probe binds to the membrane,
In females, the effect of the mutation may be then the probe sequence is present in the sample.
masked by the second copy of the X chromosome.
spectral karyotype (SKY): Spectral karyotype
shotgun sequencing: Shotgun sequencing is a (SKY) is a karyotype in which the homologous
laboratory technique for determining the DNA pairs of chromosomes are manipulated in such
sequence of an organism’s genome. The method a way that they have distinctive colors. The SKY
involves breaking the genome into a collection technique makes it easier for scientists to detect
of small DNA fragments that are sequenced chromosomal abnormalities than they can with a
individually. A computer program looks for conventional karyotype.
overlaps in the DNA sequences and uses them
to place the individual fragments in their stem cell: A stem cell is a cell with the potential to
correct order to reconstitute the genome. form many of the different cell types found in the
body. When stem cells divide, they can form more
sickle cell disease: Sickle cell disease is a stem cells or other cells that perform specialized
hereditary disease seen most often among people functions. Embryonic stem cells have the potential
of African ancestry. Caused by mutations in one to form a complete individual, whereas adult stem
of the genes that encode the hemoglobin protein, cells can only form certain types of specialized
the disease is inherited as an autosomal recessive cells. Stem cells continue to divide as long as the
trait. The mutation causes the red blood cells individual remains alive.
to take on an unusual sickle shape. Individuals
affected by sickle cell disease are chronically stop codon: A stop codon is a trinucleotide
anemic and experience significant damage to sequence within a messenger RNA (mRNA)
their heart, lungs, and kidneys. molecule that signals a halt to protein synthesis.
The genetic code describes the relationship
single nucleotide polymorphisms (SNPs): Single between the sequence of DNA bases (A, C, G,
nucleotide polymorphisms (SNPs) are a type of and T) in a gene and the protein it encodes.
polymorphism involving variation of a single base The cell reads the sequence of the gene in
pair. Scientists are studying how single nucleotide groups of three bases. Of the 64 possible
polymorphisms, or SNPs (pronounced “snips”), in combinations of three bases, 61 specify an
the human genome correlate with disease, drug amino acid and 3 are stop codons.
response, and other phenotypes.
substitution: Substitution is a type of mutation
somatic cells: A somatic cell is any cell of the where one base pair is replaced by a different
body except sperm and egg cells. Somatic cells base pair. The term also refers to the replacement
are diploid, meaning that they contain two sets of of one amino acid in a protein with a different
chromosomes, one from each parent. Mutations amino acid.
in somatic cells can affect the individual, but
they are not passed on to offspring.
59
Glossary
Human Genetic Variation
60
tumor suppressor gene: A tumor suppressor western blot: Western blotting is a laboratory
gene directs the production of a protein that is technique used to detect a specific protein in
part of the system that regulates cell division. a blood or tissue sample. The method involves
The tumor suppressor protein plays a role in using gel electrophoresis to separate the sample’s
keeping cell division in check. When mutated, proteins. The separated proteins are transferred
a tumor suppressor gene is unable to do its job, out of the gel to the surface of a membrane. The
and as a result, uncontrolled cell growth may membrane is exposed to an antibody specific to the
occur. This may contribute to the development target protein. Binding of the antibody is detected
of a cancer. using a radioactive or chemical tag. A western
blot is sometimes used to diagnose disease.
uracil: Uracil (U) is one of four chemical bases
that are part of RNA. The other three bases X chromosome: The X chromosome is one of two
are adenine (A), cytosine (C), and guanine (G). sex chromosomes. Humans and most mammals
In DNA, the base thymine (T) is used in place have two sex chromosomes, X and Y. Females
of uracil. have two X chromosomes in their cells, while
males have X and Y chromosomes in their cells.
vacuole: A vacuole is a membrane-bound cell Egg cells all contain an X chromosome, while
organelle. In animal cells, vacuoles are generally sperm cells contain an X or a Y chromosome.
small and help sequester waste products. In plant This arrangement means that during fertilization,
cells, vacuoles help maintain water balance. the male determines the sex of the offspring.
Sometimes a single vacuole can take up most
of the interior space of a plant cell. X-linked: X-linked is a trait where a gene is
located on the X chromosome. Humans and
vector: A vector is any vehicle, often a virus or other mammals have two sex chromosomes, the
a plasmid, that ferries a desired DNA sequence X and the Y. In an X-linked or sex-linked disease,
into a host cell as part of a molecular cloning it is usually males that are affected because they
procedure. Depending on the purpose of the have a single copy of the X chromosome that
cloning procedure, the vector may assist in carries the mutation. In females, the effect of
multiplying, isolating, or expressing the the mutation may be masked by the second
foreign DNA insert. copy of the X chromosome.
virus: A virus is an infectious agent that occupies Y chromosome: The Y chromosome is one of two
a place near the boundary between the living and sex chromosomes. Humans and other mammals
the nonliving. It is a particle much smaller than have two sex chromosomes, the X and the Y.
a bacterial cell, consisting of a small genome of Females have two X chromosomes in their cells,
either DNA or RNA surrounded by a protein coat. while males have X and Y chromosomes in their
Viruses enter host cells and hijack the enzymes cells. Egg cells contain an X chromosome, while
and materials of the host cells to make more sperm cells contain an X or a Y chromosome.
copies of themselves. Viruses cause a wide variety This arrangement means that during fertilization,
of diseases in plants and animals, including the male determines the sex of the offspring.
AIDS, measles, smallpox, and polio.
61
Glossary
Human Genetic Variation
yeast artificial chromosome (YAC): Yeast zebrafish: The zebrafish is a member of the
artificial chromosome (YAC) is a human- minnow family. It is a model organism used to
engineered DNA molecule used to clone DNA study the development of vertebrates because
sequences in yeast cells. YACs are often used in the embryo is transparent, it develops outside its
connection with the mapping and sequencing of mother, and its development from egg to larva
genomes. Segments of an organism’s DNA, up to happens in just three days.
1 million base pairs long, can be inserted into
YACs. The YACs, with their inserted DNA, are
then taken up by yeast cells. As the yeast cells
grow and divide, they amplify the YAC DNA,
which can be isolated and used for DNA
mapping and sequencing.
62
L E S S O N 1
Engage
Alike, But Not
the Same
Focus At a Glance
Students conduct a classwide inventory of human traits, construct
histograms of the data they collect, and play a brief game that introduces
the notion of each individual’s uniqueness.
Major Concepts
Humans share many basic characteristics, but there is a wide range
of variation in human traits. Most human traits are multifactorial:
They are influenced by multiple genes and environmental factors.
Objectives
After completing this lesson, students will
• understand that they share many traits;
• understand the extent of genetic similarity and variation among humans;
• be able to explain that most human traits are multifactorial, involving
complex interactions of multiple genes and environmental factors; and
• understand that genetic variation can be beneficial, detrimental,
or neutral.
Prerequisite Knowledge
Students should be familiar with constructing and interpreting histograms.
63
Human Genetic Variation
One goal of the Human Genome Project was to provide the complete
sequence of the human genome. Another goal was to illuminate the extent
of human genetic variation by providing a detailed picture of human
similarities and differences at the molecular level. Research indicates that
any two individuals are 99.9 percent identical at the level of their DNA.
The 0.1 percent where we vary from one another (about 1 out of 1,000
DNA bases) is clearly very important. It is within this small fraction of
the genome that we find clues to the molecular basis for the phenotypic
differences that distinguish each one of us from all others.
In this lesson, students are introduced to the notion that although we are
very similar to one another, we are also very different and our differences
reflect a complex interplay between genetic and environmental factors.
This understanding sets the stage for subsequent lessons in the module in
which students learn about the molecular differences that help explain our
phenotypic differences and also consider some of the medical and ethical
implications of scientists’ growing understanding of these differences.
Web-Based Activities
In Advance None.
Construct four sets of axes on the board or the classroom wall (use masking
tape). Label the axes as shown in Figure 7.
64
Figure 7. Construct the four sets of axes shown here on the board or on a wall of your classroom.
1. Begin the lesson by telling the class something like, “If a visitor from
another planet walked into this classroom, he might easily conclude
Procedure
that humans all look very much alike.” If students complain that this
is not true, answer with something like, “You certainly are more like
one another than you are like this plant [point to the plant]. Or this
fish [point to the fish]. And for sure, you are more alike than any one
of you is like the bacteria on this slide [wave the prepared slide of
bacteria in the air]. Humans—Homo sapiens—have a set of traits that
define us as a species, just like all other species have a set of traits
that define them.”
2. Continue the lesson by saying, “Let’s see just how similar you are.”
Give one copy of Master 1.1, An Inventory of a Few Human Traits,
to each student and ask students to work in pairs to complete it.
cross left thumb over right: Natural tendency is to cross left thumb
over right when clasping hands together.
65
Student Lesson 1
Human Genetic Variation
If you constructed the axes on the board, students can use chalk to
record their data. If you used masking tape to construct the axes on the
wall, ask students to record their data by taping one 3 × 5 card in the
appropriate place on each set of axes.
Tip from the field test: You may wish to give males one color of chalk or
3 × 5 card to use in recording their data and females a different color.
This strategy will allow the class to determine whether any of the three
characteristics other than sex (for example, height) shows differences
related to sex.
4. After the students have finished collecting and recording their data,
ask them to look at the four histograms they built and identify what
evidence they see in those data that they share many traits with other
members of their class.
Students may answer that all people have only one nose, and all people
are only one sex or the other.
5. Continue the lesson by saying, “But now that I look around the room,
it is clear that you are different. What evidence do you see in these
data that people are different?”
Students should recognize that not everyone is the same height and not
everyone has the same hair color.
As students look at the data, you may wish to ask them to compare the
shapes of the histograms for sex and height. The sex histogram has two
distinct peaks because there are only two categories of individuals—
female and male. That is, sex is a discontinuous trait. In contrast, height
is a continuous trait that has many categories of individuals, ranging
from very short to very tall. The shape of the height histogram may
begin to approach a bell curve, or normal distribution. It may also have
two peaks—a bimodal distribution—with one peak representing the
female students and the other representing the males.
66
7. Conduct the game described below with several volunteers.
• Choose a volunteer to determine his or her “uniqueness” as
compared with the other students.
• Ask all students to stand.
• Invite the volunteer to begin to identify his or her phenotype for
each of the 13 human traits listed on Master 1.1, An Inventory
of a Few Human Traits. Begin with the first trait and proceed
sequentially. As the volunteer lists his or her phenotype for each
trait, direct the students who share the volunteer’s phenotype
for that trait to remain standing. Direct all other students to sit.
• Continue in this fashion until the volunteer is the only person
still standing. Count how many traits the class had to consider
to distinguish the volunteer from all other students in the class.
Compare this number with the students’ predictions.
• Repeat as desired with another volunteer.
Question 1. Some human traits can be changed by human intervention, Collect and review the
and some cannot. Provide examples of each of these types of traits.
students’ completed
Biological sex and blood type cannot be changed. Hair color, skin Master 1.2 to assess their
color, and even height and mental abilities can be changed by human understanding of the
intervention. Students also may suggest that body piercing alters lesson’s major concepts.
human traits.
Question 2. You probably already know that some traits are genetic and
others are environmental. But most human traits reflect an interaction
between genetic and environmental factors. Name some traits that might
fall into this category and explain why you think they do.
Height, weight, intelligence, and artistic or athletic ability are examples Increasing evidence
of traits that are influenced by genetic and environmental factors. Some indicates that all human
students may mention disorders such as certain types of cancer or diseases have genetic and
even psychiatric disorders. We know that these types of traits are
environmental
both genetic and environmental because we see evidence that they
run in families and because we know we can modify them by components. Point out
changing the environment. that diseases such as
cancer, heart disease, and
Question 3. Describe some of the benefits of human genetic variation. diabetes are traits that
What are some of the potential problems that such variation can cause? show an interaction
between genetic and
Students may mention a number of benefits, such as allowing people
to be distinguished from one another and increasing the diversity of environmental factors.
abilities, interests, and perspectives among humans. Some students may Students will consider
recognize that genetic variation also benefits the species because it is this concept in Lesson 4,
the basis for evolution by natural selection. Students will consider this Are You Susceptible?
aspect of variation in Lesson 2, The Meaning of Genetic Variation.
67
Student Lesson 1
Human Genetic Variation
You may wish to point out that research reveals that more variation
exists within populations than between them (Figure 4, page 22). As
noted in “Understanding Human Genetic Variation” (pages 19–29), an
examination of human proteins demonstrated that about 85 percent
of all variation occurred within populations, whereas only 15 percent
occurred between populations. That is, we are more “like” people with
other ethnic or geographic origins than we might think.
68
This lesson introduces students to several ideas that you may wish them to Potential
explore in more depth. For example, assign students to use their textbooks
to identify the biological mechanisms that lead to and maintain diversity Extensions
in populations.
69
Student Lesson 1
Human Genetic Variation
Lesson 1 Organizer
Procedure
What the Teacher Does
Reference
Tell the class something like this: “If a visitor from another planet Page 65
walked into this classroom, he might easily conclude that humans all Step 1
look very much alike.”
Ask, “Do you agree with this statement?” Use examples to help
students recognize that humans are more similar to each other than
they are to other species and that humans have a set of traits that
define us as a species.
Invite students to explore similarities among classmates. Give each Page 65
student one copy of Master 1.1 and ask them to work in pairs to Step 2
complete it.
Define terms (on page 65) if unfamiliar to students.
Ask students to enter data from their copy of Master 1.1 onto Page 66
graphs you prepared on the board. Step 3
Have class analyze data on graphs and identify evidence that Page 66
supports the idea that students share many traits with other class Step 4
members.
Continue by pointing out that you can see that individuals are Page 66
different. Ask students, “What evidence supports that people are Step 5
different?”
Ask students how many traits they would need to consider to Page 66
identify a given student as unique. Write predictions on the board. Step 6
Conduct the game described in Step 7 to determine uniqueness Page 67
among class members. Step 7
Give each student a copy of Master 1.2. Ask students to work in Page 67
pairs to answer the questions. Discuss answers with the class (on Step 8
pages 67 to 68).
Ask, “What has this lesson illustrated about how one human Page 68
compares with another human? What has it illustrated about human Step 9
variation in general?” Ask students to summarize their ideas and
share with the class.
70
L E S S O N 2
Explore
The Meaning of
Genetic Variation
Focus At a Glance
Students investigate variation in the beta globin gene by identifying
base changes that do and do not alter function, and by using several
Web- or print-based resources to consider the significance in different
environments of the base change associated with sickle cell disease.
Major Concept
The ultimate source of genetic variation is differences in DNA sequences.
Most of those genetic differences do not affect how individuals function.
Some genetic variation, however, is associated with disease, and some
improves the ability of the species to survive changes in the environment.
Genetic variation, therefore, is the basis for evolution by natural selection.
Objectives
After completing this lesson, students will
• recognize that the extent of molecular variation between two people
is only about 0.1 percent, but because of the large size of the human
genome, this translates to about 3 million base differences;
• understand that most human genetic variation does not appear to
affect function;
• be able to explain that some human genetic variation is related to
disease and provide an example; and
• be able to describe a benefit of human genetic variation and relate
this benefit to human evolution by natural selection.
Prerequisite Knowledge
Students should understand basic Mendelian patterns of inheritance,
especially autosomal-recessive inheritance; the basic structure of DNA;
the transcription of DNA to messenger RNA; and the translation of
messenger RNA to protein.
71
Human Genetic Variation
change in a single base pair and the symptomology of sickle cell disease.
Similarly, our understanding of the basic biochemical mechanisms
underlying the symptoms associated with sickle cell disease has provided
important clues about possible strategies for clinical intervention. You
may wish to make some of these points with your students as they
complete the lesson.
Day 1, Step 12, describes an optional laboratory exercise that you may wish
to conduct to enrich your students’ understanding of molecular variation
and the methods by which it can be identified and studied. Information
about the materials you’d need is on page 77.
Follow the instructions on page 77 to get to the Web site students will use
to view the video documentary (Step 12). If you do not have Internet access,
you can use the print-based alternative (also discussed on page 77).
72
DAY 1 Procedure
1. Introduce the lesson by asking students to identify the ultimate source
of the variation they investigated in Lesson 1.
The beta globin gene is one of the smallest human genes that encode
a protein; the entire gene has only about 1,700 nucleotide pairs and
includes just two introns. The sequences on Masters 2.1 and 2.2 do not
show the gene’s promoter regions but begin with the first sequences
that are translated.
3. Ask students to read the paragraph at the top of each page and then
estimate the total number of bases on each page. Direct students to
write their estimate in the space provided on the masters.
The total number of bases on each page is 1,691. Students will need this
number to complete their calculations in Step 6.
73
Student Lesson 2
Human Genetic Variation
4. Remind the students that the sequences on the masters come from the
beta globin gene in two different people. Ask students what they notice
when they compare the sequence from person A with the sequence
from person B.
5. Point out that this sequence is only 1,691 bases long and the complete
human genome is about 3 billion bases long. Ask the students how
they might use the sequences from person A and person B and the
total size of the human genome to estimate the extent of variation
(the number of bases that differ) between the two people B. Ask as
well what assumption they would be making as they arrived at
their estimate.
Students could estimate the extent of variation across the entire genome
by calculating the percentage of difference between the two sequences
shown for person A and person B, and then multiplying this percentage
by 3 billion (the approximate number of bases in the human genome).
This estimate assumes that the sequence shown displays a typical
amount of variation.
6. Give one copy of Master 2.3, How Much Variation? Doing the Math, to
each student and direct the students to use the master as a guide to
estimate this value.
If your students need help completing this estimate, suggest that they
first try the example at the bottom of the master.
Note that the actual number of base differences between two people is
likely somewhat higher than this because this estimate, based as it is
on the approximate size of the human genome (one copy of each of the
autosomes, plus the X, Y, and mitochondrial chromosomes), does not
take into consideration the fact that humans are diploid.
74
7. Ask students what their estimates indicate about the extent of human
genetic variation at the molecular level.
Students should recognize that at the molecular level, humans are far
more alike (about 99.9 percent of the bases are the same) than they are
different (only about 0.1 percent of the bases are different). Students
should also realize, however, that even a small percentage difference
can represent a very large actual number of differences in something
as large as the human genome.
8. Explain that the rest of the lesson focuses on this 0.1 percent
difference between people. Ask students questions such as, “Do you
think these differences matter? What effect do you think they have?
What might affect how much a specific difference matters?”
9. Explain that studying the beta globin gene more closely will help
students begin to answer these questions for themselves. Have
students examine the sequences on Master 2.1, Beta Globin Gene—
Person A, and Master 2.2, Beta Globin Gene—Person B, again. Explain
that the regions that show bases grouped in triplets are from the
coding regions (exons) of the gene, while the other regions are from
the noncoding regions (introns). Then, ask students which of the
two base differences in bold is most likely to matter, and why.
75
Student Lesson 2
Human Genetic Variation
10. Explain that although 3 million base differences sounds like a lot,
most of these differences have no significant impact on individuals,
either because they occur in a noncoding region or for another reason.
Point out that most of these 3 million differences can only be detected
A major concept by examining the DNA sequence.
that students should
understand from Day 1 Students should now understand that while some base differences occur
of the lesson is that in coding regions and may result in an altered amino acid sequence
most genetic differences in the protein coded for by a gene, others occur in noncoding regions
where they likely have no impact. Point out that only a small percentage
do not affect how
of the DNA sequences in the human genome are coding sequences.
individuals function. Furthermore, only a small percentage of the noncoding DNA sequences
are regulatory sequences such as promoters or enhancers that can
influence the amount of gene product that results from a given gene.
The remaining DNA sequences (the majority of the total DNA sequences
in the genome) have no known function. Most of the variations in DNA
sequence occur in these latter sequences and have no detectable impact.
Note: You may wish to clarify for students the reason that most
molecular variation occurs in noncoding regions. It is true that there
are more noncoding than coding regions. However, the fundamental
biological reason for the increased variability of noncoding regions is
that there is no selective pressure exerted on changes in them. Point
out that some differences that occur in noncoding regions do have an
impact. For example, several mutations within introns in the beta globin
gene cause incorrect splicing of the messenger RNA, and as a result,
several codons may be inserted into or omitted from the sequence,
leading to nonfunctional beta globin polypeptides.
11. Point out the codon in which the first difference between the
two sequences occurs and tell students that person A has normal
hemoglobin, while person B has abnormal hemoglobin that is
associated with sickle cell disease. Explain that the single base
difference in this codon determines whether a person has normal
hemoglobin or sickle hemoglobin.
If you wish, ask students to identify the actual amino acid difference
between these two types of hemoglobin, based on the difference in the
DNA sequence of the codon you identified. This is an opportunity for
76
students to review the translation process and the genetic code. Remind
them that the sequence they have is the same as the messenger RNA
sequence, except it has Ts where the RNA would have Us. Normal
hemoglobin has glutamic acid (RNA codon GAG) in the position where
sickle cell hemoglobin has valine (RNA codon GUG).
12. Step 12 for classes with access to the Internet: Tell students
that in the next part of the lesson, they will consider the
consequences of the genetic variation that results in sickle
cell disease. Hand out Master 2.4, Exploring Sickle Cell
Disease, and direct students to organize into small groups. Have
students view the documentary “What Is Sickle Cell Disease?” on
the student section of the Human Genetic Variation Web site
(http://science.education.nih.gov/supplements/genetic/student; click
on “The Meaning of Genetic Variation”) and begin working on the
questions.
13. When students reach Question 2 on Master 2.4, they should explain
how they intend to test the Lindsey twins. Give the group a copy
of the test results (Master 2.6, Results of the Lindsey Test) after the
students correctly explain the test they would have conducted.
77
Student Lesson 2
Human Genetic Variation
DAY 2
Question 1a. What are the primary symptoms of sickle cell disease?
What happens in a person’s body to cause these symptoms?
Sickle hemoglobin (Hb S) has the amino acid valine in the position
where normal hemoglobin (Hb A) has the amino acid glutamic acid.
Question 1d. What does this difference in hemoglobin tell you about the
DNA of people whose cells make Hb S as compared with people whose
cells make Hb A?
The sequence of DNA that codes for hemoglobin in people whose cells
make Hb S must be different from the sequence of DNA that codes for
hemoglobin in people whose cells make Hb A. The allele that codes for
Hb A has the nucleotide A at a place where the allele that codes for Hb S
has the nucleotide T.
Question 1e. What is the difference between sickle cell disease and sickle
cell trait? Demonstrate in your answer that you understand how sickle
cell disease is inherited.
People who have sickle cell disease have inherited two alleles for sickle
cell hemoglobin, one from each of their parents. They are homozygous
for the sickle cell hemoglobin allele. People who have sickle cell trait
78
have inherited one allele for sickle cell hemoglobin from one parent
and one allele for normal hemoglobin from the other parent. They are
heterozygous and usually have no symptoms.
Question 2. Use what you learned about sickle cell disease and trait to
propose a way to determine whether Ms. Lindsey’s twins have sickle cell
trait. Explain your procedure to your teacher, then use the information
provided on the handout your teacher will give you to determine the
results of the test. Highlight the contribution
of basic science to the
Students should explain the following procedure: Collect DNA from improvement of personal
Jason and from Sondra and treat it for analysis of alleles of the beta
and public health by
globin gene. Use gel electrophoresis to visualize the alleles present
in each twin’s DNA. “Standards,” or controls, of DNA from people asking your students
with the normal (Hb A) and sickle (Hb S) alleles should be included whether an early-20th-
for comparison. (Unless you have previously discussed restriction century physician would
enzymes and RFLP analysis, you probably do not want to introduce have answered Ms.
these concepts here. Instead, just explain to students that DNA isolated Lindsey’s question in this
from individuals can be treated in ways that make different alleles show manner. The answer, of
different gel electrophoresis patterns.)
course, is no. The first
If a twin has normal hemoglobin, his or her DNA will migrate on observation of sickle-
the gel in the same pattern as the DNA standard for the Hb A allele. shaped cells was made in
If a twin has sickle cell disease, his or her hemoglobin will migrate 1910, but the molecular
in the pattern of the DNA standard for the Hb S allele. If a twin is basis of the disease was
heterozygous (has sickle cell trait), his or her DNA will contain two not worked out until
different alleles for the hemoglobin gene and show both the pattern
1949. You may also note
of the Hb A standard and the pattern of the Hb S standard.
that direct diagnosis of
Some students may suggest an alternative procedure that uses gel this disease through DNA
electrophoresis with hemoglobin proteins from the twins’ blood to reveal analysis of a person’s
their genotypes. Hb A and Hb S migrate differently in an electrical field genotype was made
because of differences in their electrical charges. Master 2.6, Results of possible in the mid-1980s.
the Lindsey Test, however, shows the results for the DNA test for different
alleles of the beta globin gene because this module focuses on DNA. If
students propose a test for the Hb A and Hb S proteins, ask them to
think about what the different proteins imply about the genes for those
proteins. Then, ask them to devise a DNA-based test instead.
2. Ask students what their study of the beta globin gene and sickle cell
disease has illustrated about human genetic variation.
3. Summarize the students’ answers by saying, “So you are saying that
most variation does not make a difference and that some variation
is negative. Is it possible that some variation is also positive?”
Entertain several answers to this question.
The only thing that would change is the implication of the findings for
the twins’ health. Jason will still have sickle cell disease, but Sondra
should have enhanced resistance to malaria.
In the case of cystic fibrosis, there is good evidence that those who
carry one CFTR allele associated with the disease have increased
resistance to typhus, a common killer in Europe in past centuries.
There is also circumstantial evidence that those who have one
allele associated with Tay-Sachs disease may be more resistant to
tuberculosis than those who are homozygous for the normal allele.
81
Student Lesson 2
Human Genetic Variation
82
Procedure
What the Teacher Does
Reference
Point out the codon in which the first difference occurs. Tell students Page 76
that person A has normal hemoglobin, while person B has abnormal Step 11
hemoglobin associated with sickle cell disease. Explain that the single
base difference in this codon determines whether the person has normal
or sickle hemoglobin.
Tell students that they will next consider the consequences of the genetic Page 77
variation that results in sickle cell disease. Give each student a copy of Steps 12, 13
Master 2.4. Direct students to form small groups to watch the online
documentary “What Is Sickle Cell Disease?” and begin working on the
questions. After groups have proposed a procedure for Question 2 on
Master 2.4, give each group a copy of the test results, Master 2.6.
Optional alternative to Master 2.6: Have students do the lab activity Page 77
themselves.
Day 2
Procedure
What the Teacher Does
Reference
Direct groups to complete or review answers to questions on Master 2.4. Page 78
Convene a class discussion in which students can share their answers. Step 1
Ask students what the beta globin gene and sickle cell disease illustrate Page 80
about human genetic variation. Step 2
Summarize students’ answers by saying, “So you are saying that most Page 80
variation does not make a difference and that some variation is negative. Step 3
Is it possible that some variation also is positive?” Allow several students
to respond.
Challenge students to imagine they are doctors practicing in Cameroon Page 80
in west-central Africa. Have students use the resources on the Web site Step 4
to compare the incidence of sickle cell disease in Cameroon with the
incidence in the United States and to determine how scientists explain
the difference.
Ask students how this information would change what they would say to Page 81
Ms. Lindsey. Step 5
Close the lesson by asking students the following questions: Page 81
• “Will natural selection favor the survival of people who produce Hb S Step 6
or people who produce Hb A?”
• “All populations have genetic variations that lead to increased
incidence of particular disorders. Why would such apparently harmful
variations have been maintained in those populations?”
83
Student Lesson 2
Human Genetic Variation
84
Procedure
What the Teacher Does
Reference
Point out the codon in which the first difference occurs. Tell students Page 76
that person A has normal hemoglobin, while person B has abnormal Step 11
hemoglobin associated with sickle cell disease. Explain that the single
base difference in this codon determines whether the person has normal
or sickle hemoglobin.
Tell students that they will next consider the consequences of the genetic Page 77
variation that results in sickle cell disease. Give each student one copy Steps 12, 13
of Masters 2.4 and 2.5. Direct students to organize into small groups
and to begin working on the questions. After groups have proposed a
procedure for Question 2 on Master 2.4, give each group a copy of the
test results, Master 2.6.
Optional alternative to Master 2.6: Have students do the lab activity Page 77
themselves.
Day 2
Procedure
What the Teacher Does
Reference
Direct groups to complete or review answers to questions on Master 2.4. Page 78
Convene a class discussion in which students can share their answers. Step 1
Ask students what their study of the beta globin gene and sickle cell Page 80
disease has illustrated about human genetic variation. Step 2
Summarize students’ answers by saying, “So you are saying that most Page 80
variation does not make a difference and that some variation is negative. Step 3
Is it possible that some variation also is positive?” Allow several students
to respond.
Challenge students to imagine they are doctors practicing in Cameroon Page 80
in west-central Africa. Have students use the Reference Database Step 4
(Master 2.5) to compare the incidence of sickle cell disease in Cameroon
with the incidence in the United States and to determine how scientists
explain the difference.
Ask students how this information would change what they would say to Page 81
Ms. Lindsey. Step 5
Close the lesson by asking students the following questions: Page 81
• Will natural selection favor the survival of people who produce Hb S Step 6
or people who produce Hb A?
• All populations have genetic variations that lead to increased
incidence of particular disorders. Why would such apparently harmful
variations have been maintained in those populations?
85
Student Lesson 2
L E S S O N 3
Explain
Molecular Medicine
Comes of Age
Focus At a Glance
Students discover some of the benefits of understanding human genetic
variation at the molecular level by assuming the roles of employees of
two fictional pharmaceutical companies to solve problems related to
the development of new drugs.
Major Concepts
One of the benefits of understanding human genetic variation at a
molecular level is its practical value for helping us understand and
treat disease. The development of effective gene-based therapies is
an exciting outcome of human genetic research. These therapies,
however, are potentially many years away for many diseases.
Objectives
After completing this lesson, students will
• appreciate that identifying and sequencing disease-related genes
helps scientists better understand and treat disease;
• be able to explain that in the future, physicians will change how they
prescribe drugs because of our increasing understanding of how
genetic differences among people affect response to drug treatment;
• be able to explain how understanding the molecular structure of a
disease-related gene can help scientists develop new strategies for
treating the disease; and
• recognize that as our understanding of human genetic variation
improves, we will likely see many changes in how physicians
diagnose and treat human diseases.
Prerequisite Knowledge
Students should understand the relationship among DNA, RNA, protein,
and amino acids, as well as how to interpret data displayed in tables.
87
Human Genetic Variation
Biologists have also long known that understanding the molecular structure
of a disease-related gene can help them identify potential targets for
intervention. As described in “Understanding Human Genetic Variation,”
a striking example of this approach to combating disease is recent work
on cystic fibrosis. Cystic fibrosis is the most common fatal genetic disease
in the United States, affecting about 30,000 people. Currently, about half
of those affected die by age 30. Since the identification in 1989 of the gene
that is altered in cystic fibrosis, the pace of basic research has increased
rapidly, and scientists are optimistic that they will be able to translate
new knowledge about the molecular basis of the disease to new strategies
to improve patients’ lives. A recent article by scientists from the National
Human Genome Research Institute is an excellent review of the history and
current state of genomic medicine (Green et al., 2011).
88
In this lesson, students assume the roles of employees of two fictional
pharmaceutical companies, Firm A and Firm B. Each company is facing a
significant challenge related to the development of a new drug. Firm A is
developing a drug to treat asthma. Unfortunately, preliminary test results
show variable and unpredictable effects. Students working as employees of
Firm A must discover an explanation for these results and recommend a
course of action. As students investigate this problem, they learn about the
relationship between genetic variation and individual responses to drugs
and discover one of the ways pharmaceutical companies are beginning to
deal with this issue.
As students investigate this problem, they learn that knowing the sequence
of a disease-related gene and understanding the disease’s biochemical basis
can help scientists develop exciting new approaches to treatment.
Because both pharmacogenomics and targeted drug therapy are still in their
early stages, this lesson is a bit futuristic and you may wish to acknowledge
this to students. It is clear, however, that the era of molecular medicine—
the application of knowledge about the molecular basis of variation to
treating human disease—is already upon us. Although molecular medicine
is just beginning to develop, the field has enormous potential for the
improvement of personal and public health.
89
Student Lesson 3
Human Genetic Variation
3. Divide the class in half and explain that one-half will act as employees
in Firm A and the other half, as employees in Firm B. Tell students
that the problems the two firms face are different, but both problems
can be solved in ways that relate to the statement on the transparency.
4. Direct students to organize into groups of four. Give one copy each of
Masters 3.2, 3.3, 3.4, and 3.5, Saving Firm A, [Role], to each group in
one-half of the class and one copy each of Masters 3.8, 3.9, 3.10, and 3.11,
Saving Firm B, [Role], to each group in the other half. Also give one copy
of Master 3.6, Report Form for Firm A, or Master 3.12, Report Form for
Firm B, to each student and explain that students should use these
forms to organize their discussions and report the results of their work.
5. Instruct the groups to decide who will assume each of the four roles
associated with their problem and to distribute the masters accordingly.
90
6. Give the groups 30 minutes to complete their reports and to be
ready to defend their analysis of their company’s problem and their
suggested solution to the class. They should use the Report Form
(Master 3.6 or 3.12) to organize their thoughts.
When students reach Step 6 on Master 3.6 or Step 5 on Master 3.12, they
will ask you, as vice president of the company, for additional data (Master
3.7, Some New Genetic Data about Firm A, or Master 3.13, Some New
Information about Firm B). You can give the groups copies of the masters, or
you can devise an approach that requires students to search for the data.
7. After 30 minutes, call the class to order. Explain that you will assume
the role of the vice president for research for Firm A first and then
the role of the vice president for research for Firm B, and that you are
calling everyone together to hear the results of the groups’ work.
8. Display a transparency of Master 3.6, Report Form for Firm A, and use
it to guide the discussion by asking groups from Firm A to present
their answers to the questions (a different group should answer each
question). After one group has offered an answer, invite questions
and additional comments from the class.
91
Student Lesson 3
Human Genetic Variation
Question 5. What does the example of ApoE (refer to Master 3.4, Saving
Firm A, Role: Molecular Biologist) suggest might be happening with
Drug X? Based on this example, what might Firm A investigate?
The data indicate that response to the Alzheimer drug might be based
on variations in the ApoE gene. Perhaps Firm A should explore genetic
differences with respect to response to Drug X.
Question 6. Firm A’s vice president for research (your teacher) will
provide you with some new data. What do the new data reveal
about Drug X?
Question 8. Has your group solved the biological problem facing the
company with respect to Drug X? What new problems has it raised?
The group’s work has answered the basic biological question about
response to Drug X. It has raised new questions about the ability to
test all asthma sufferers. For example, how expensive is it to do that?
Will physicians order the test? Will it be covered by health insurance?
Who will have access to the information that results from the genetic
test? How will Firm A educate physicians and other healthcare
professionals so they understand the test and the results and can
explain this information to their patients?
92
9. Repeat the same process with the groups from Firm B, but use a
transparency made from Master 3.12 to guide the discussion.
Drug Y is a successful treatment for cystic fibrosis (CF) and the firm’s
leading product. Firm B needs to keep looking ahead, however, and
begin thinking about new treatments for CF that take advantage
of what scientists have learned about the condition and, in the
future, might be able to supplement or even replace income that the
company is now receiving from Drug Y.
93
Student Lesson 3
Human Genetic Variation
Question 5. Firm B’s vice president for research (your teacher) will
provide you with some new information. What clue does this new
information provide about how Firm B might approach developing
new treatments for CF?
The important clue that students should gain from this new
information is that understanding the biological basis of CF has
allowed these researchers to propose a way to correct the problem in
CF cells. This approach is different from treating its consequences.
Question 7. Has your group solved the problem facing the company
with respect to Drug Y? What new problems has it raised?
No, the group has not solved the problem facing the company, but it has
You may wish to ask the suggested several directions that the company may want to investigate
students who worked on as it develops new CF treatments. New problems that the group’s work
Firm A’s problem to has raised include problems common to all development of new drugs:
answer the questions deciding on an approach to try, allocating funds to pay for development
related to Firm B’s and clinical testing, and going through the process of gaining Food and
problem, and vice versa. Drug Administration (FDA) approval for the new treatment.
94
10. Challenge students to generalize what they have learned by answering
the following questions:
11. Display again the transparency you made from Master 3.1, Molecular
Medicine Comes of Age. Ask students to explain what it means, and
provide examples that illustrate or serve as evidence for this point.
12. Close the lesson by asking students what they think the
transparency’s title means.
95
Student Lesson 3
Human Genetic Variation
Lesson 3 Organizer
Procedure
What the Teacher Does
Reference
Display a transparency of Master 3.1. Ask students what they think the Page 90
statement means and whether they can think of examples that illustrate or Step 1
provide evidence for this statement.
Explain that to investigate this statement, students will work in groups as Page 90
employees of two pharmaceutical companies that are facing problems. Step 2
Have one-half the class act as employees in Firm A and the other half, in Page 90
Firm B. Tell students that the two companies face different problems, but Step 3
both problems can be solved in ways that relate to the statement on the
transparency.
Direct students to work in groups of four. Give each group that will work Page 90
as Firm A a copy of Masters 3.2, 3.3, 3.4, and 3.5. Give each group that will Step 4*
work as Firm B one copy of Masters 3.8, 3.9, 3.10, and 3.11. Give each student
a copy of either Master 3.6 (Firm A) or Master 3.12 (Firm B) and explain that
these forms will help them organize their discussions and report their results.
Instruct groups to decide who will play each of the four roles and to Page 90
distribute the masters accordingly. Step 5
Allow 30 minutes for groups to complete their reports on Master 3.6 or Page 91
3.12. When students ask for additional data, give them Master 3.7 or 3.13. Step 6*
At the end of that time, groups should be ready to defend their analysis
and to present their suggested solution to the class.
Call the class to order. Explain that you will assume the role of vice Page 91
president for research first for Firm A and then for Firm B. Step 7
Display a transparency of Master 3.6. Use it to guide the discussion about Page 91
Firm A. After Firm A groups share their ideas, ask if other class members Step 8
have questions or comments.
Display a transparency of Master 3.12. As before, use it to guide the Page 93
discussion about Firm B. Step 9
Challenge students to use these questions to generalize what they learned: Page 95
• How is genetic variation related to the use of drugs? Step 10
• How will pharmaceutical companies likely use our increasing
understanding of human genetic variation?
• How can discovering the genes associated with genetic disorders help
scientists develop new approaches to treatment?
Display again the transparency of Master 3.1. Ask students to explain the Page 95
statement and provide examples. Step 11
Close the lesson by asking students what they think the title on the Page 95
transparency of Master 3.1 means. Step 12
Focus
Students play a game to explore the relationship between genetic At a Glance
variation and environmental factors in the onset of heart disease
and consider the implications for disease prevention of increased
knowledge about genetic variation.
Major Concepts
Studying the genetic and environmental factors involved in multifactorial
diseases will lead to better diagnosis, prevention, and treatment.
Objectives
After completing this lesson, students will
• understand that all disease, except perhaps trauma, has both a
genetic and environmental component;
• recognize that certain behaviors can increase or reduce a person’s
risk of experiencing certain medical outcomes; and
• understand that the ability to detect genes associated with common
diseases increases the prospects for prevention.
Prerequisite Knowledge
Students should understand the concept of a gene.
97
Human Genetic Variation
Introduction Lesson 3, Molecular Medicine Comes of Age, and Lesson 4, Are You
Susceptible?, focus students’ attention on the practical, medical applications
of understanding human genetic variation at a molecular level. Lesson 3
looks at treatment options that become possible with the discovery and
sequencing of a disease-related gene. In contrast, Lesson 4 focuses on the
likelihood that genetic testing for common, multifactorial diseases will
increase in the future and invites students to consider the prospects that
this information will help individuals make wise decisions about their
personal health. Specifically, Lesson 4 uses heart disease as an example
of the common, multifactorial diseases that constitute the bulk of the
healthcare burden in the United States and other developed countries.
The lesson builds on the treatment of variation in the previous lessons
and sets up the discussion of ethics that is central to Lesson 5, which
deals with genetics and cancer.
For the most part, the treatment of genetics in high school focuses on single-
gene traits. In addition, most of the single-gene traits discussed are disorders,
because they provide reasonably straightforward examples of Mendelian
patterns of inheritance. Research in human genetics, however, increasingly
addresses multifactorial traits, that is, traits that result from the interaction
of multiple genes and environmental factors. Among the multifactorial
traits that come most quickly to mind are behavioral characteristics that
are controversial and that often attract media attention—for example,
intelligence, sexual preference, aggression, and basic personality traits such
as novelty-seeking behavior or shyness. Research into the relative genetic
and environmental contributions to behavioral traits has been uneven and
is confounded by the difficulty of defining and measuring the phenotypes
in question with any degree of accuracy and reliability.
98
Our knowledge of the biological relationship between gene and phenotype
is much less certain for multifactorial diseases. It is clear, for example,
that genetic factors contribute to the risk for early onset heart disease, but
the exact relationship is as yet unclear, as is the case for the relationship
between certain genetic markers and the risk of schizophrenia. In these
cases, the distance between gene—or genes—and phenotype is greater than
it is in single-gene disorders, probably because of a host of environmental
variables whose influences on phenotype are difficult to discern.
Genetic testing for common, multifactorial diseases will affect more people
than does testing for relatively rare, single-gene disorders. Many of the same
ethical and policy questions will apply—privacy and confidentiality, for
example—but the uncertainty inherent in genetic testing for multifactorial
diseases will introduce some new challenges for the public, chief among
them the notions of susceptibility and risk. You may learn from a “positive”
test that you are susceptible to developing the disease in question, but
that will not mean that you are destined to develop the disease. Nor will
a “negative” test mean that you definitely will not develop the disease. In
addition, while you may learn that there is an increased relative risk of
developing a given disease—that is, a risk that is increased above the risk
for the general population—the absolute risk may still be quite low.
99
Student Lesson 4
Human Genetic Variation
Procedure 1. Begin the lesson by asking students to suggest definitions of the term
“risk.” You might prompt the discussion by asking students to think
about risky behaviors that are a part of adolescence. Write three or
four of the definitions on the board.
Students may suggest that “risk” refers to the chance that something
bad or negative will happen, as, for example, the risk involved with
dangerous behaviors. Help students see that one way to think about
risk is in terms of one’s chance of experiencing a particular event.
For example, if a person performs aerial acrobatics on skis, he or
she has some risk of getting hurt.
2. Ask students whether they think risks can be modified. For example,
ask them if there is any way they can modify their risk of being
robbed or their risk of a heart attack or of getting cancer.
Source: Courtesy of Sinauer Associates, Inc., from E.P. Mange and A.P.
Mange: Basic Human Genetics, Second Edition, 1999.
4. Explain that Sergei Grinkov was born with a mutation called PL(A2)
in a single gene that affects the formation of blood clots. The mutation
causes clots to form in the wrong places at the wrong time. If such
a clot forms in one of the arteries that supply the heart, a heart
attack can result. Ask students to consider whether this mutant
allele influenced Sergei Grinkov’s risk of a premature heart attack.
100
of the population. One may have an elevated relative risk but still have
a low absolute risk. For example, one may have an increased risk of 20
percent above the risk for the general population, but may still only
have a 5 percent risk of suffering the disease in question by, say, age 50.
5. Ask the class to suggest ways that Sergei Grinkov could have modified
his behavior had he known he was at increased risk for premature
heart attack.
7. Give each student one copy of Master 4.1, Rolling the Dice, and direct
students to work in groups of three to play the game described.
9. Ask students how the game is and is not like real life.
The game is like real life in that life expectancy depends on many
risk factors. The game is not like real life because students rolled the
die to determine what their risk factors would be instead of making
personal choices. The game also involved only environmental risk
factors, not genetic ones. If students fail to mention that the game
does not address genetic risk factors, try to elicit that response by
asking about Sergei Grinkov.
101
Student Lesson 4
Human Genetic Variation
Question 4. Think about the choices you made in each life stage.
No, some of the choices carried greater risks than others, and some
decreased the risks.
102
c. Were the risk factors associated with the choices reversible?
No, some genetic factors had negative effects, some were neutral, and
some provided protection.
103
Student Lesson 4
Human Genetic Variation
Question 7. We know about only a few genes that affect the likelihood of
a heart attack, and we have the ability to test for even fewer of them. In
the future, we certainly will learn about more of these genes. How will
increased knowledge of the genetic factors associated with heart disease
have a positive impact on individuals and society? How will it have a
negative impact?
104
Lesson 4 Organizer
Procedure
What the Teacher Does
Reference
Ask students to suggest definitions for the term “risk.” Ask students Page 100
to think about risky behaviors that are part of adolescence. Write Step 1
several definitions on the board.
Ask students whether they think risks can be modified. Page 100
Step 2
Read aloud the story on page 100, “Death of an Olympic Champion.” Page 100
Step 3
Explain that Grinkov was born with a mutation called PL(A2) in a Page 100
single gene that affects the formation of blood clots. The mutation Step 4
causes clots to form in the wrong places at the wrong time. If such
a clot forms in one of the arteries that supply the heart, a heart
attack can result. Ask students to consider whether this mutant allele
influenced Grinkov’s risk of a heart attack.
Ask the class to suggest ways that Grinkov could have modified his Page 101
behavior if he had known he was at increased risk for premature Step 5
heart attack.
Explain that premature heart attacks resulting from single-gene Page 101
disorders are uncommon. Most heart attacks occur later in life and Step 6
result from a combination of genetic and environmental factors.
Tell students that they will now explore medical risk and learn how
genetic analysis is helping us understand and define risk in new ways.
Give each student a copy of Master 4.1. Have students work in groups Page 101
of three to play the game. Step 7
Ask how many students suffered a fatal heart attack. Record on the Page 101
board the life stages at which the heart attacks occurred. Step 8
Ask students how the game is and is not like real life. Page 101
Step 9
Acknowledge the importance of genetic risk factors in the Page 102
development of heart disease. Ask students how factoring this Step 10
information into the game could affect the outcome.
Give one relevant-genes envelope to each student, and explain that it Page 102
contains information about their genetic risk for a fatal heart attack. Step 11
Ask students to open the envelopes and share their heart points until
you have addressed all four values: –10, 0, +10, and +40. Point out
that genetic risk falls off rapidly as genetic relatedness decreases.
Explain that this is the case generally for multifactorial diseases.
105
Student Lesson 4
Human Genetic Variation
Procedure
What the Teacher Does
Reference
Give each student a copy of Master 4.2. Ask students to complete Page 102
the master to compare the results of the game with and without Step 12
considering genetic factors.
Conclude the lesson by asking groups to answer one of the questions Page 102
on Master 4.2. Invite other groups to contribute additional thoughts Step 13
or challenge ideas.
106
L E S S O N 5
Evaluate
Making Decisions
in the Face of
Uncertainty
Focus At a Glance
Students analyze a case study about a family’s decisions related to testing
for particular genetic variations that increase susceptibility to breast cancer
and consider how understanding the related science can help people make
decisions in uncertain circumstances.
Major Concepts
Our growing understanding of human genetic variation will allow us to
identify genes that are associated with common diseases such as cancer.
Genetic testing to identify individuals who have variations that make them
susceptible to certain diseases can help people make decisions in uncertain
circumstances and holds the prospect for more effective prevention and
treatment. However, this capability also raises difficult questions that
illustrate the personal and social implications of biological research.
Objectives
After completing this lesson, students will
• recognize that our understanding of science can help us analyze and
make decisions in uncertain circumstances;
• understand that the ability to identify susceptible individuals through
genetic screening and testing holds the prospect for more effective
prevention and treatment;
• understand that our ability to identify individuals susceptible to
particular diseases also raises difficult questions about the uses
of genetic information;
• be able to explain that although it is possible to analyze these questions
rationally and civilly, people still may disagree on the answers; and
• understand that science can tell us what we can and cannot do, but we
depend on an analysis of ethics and public policy (informed by a sound
understanding of the science) to help determine what we should do.
Prerequisite Knowledge
Students should understand that cancer is characterized by uncontrolled
growth of cells. Students should also understand that all cancer is
fundamentally genetic because it results from the loss of genetic control of
the cell cycle. That does not mean that all cancer is hereditary. The form of
107
Human Genetic Variation
breast cancer that this lesson addresses is one of the hereditary cancers,
but it is responsible for only about 5 percent of all breast cancers. Most
breast cancers arise from somatic mutations and thus are not hereditary.
Introduction This lesson offers students the opportunity to apply their understanding
of human genetic variation to a fictional case study involving a potentially
painful set of decisions that various members of a family have to make.
Groups of students analyze the case of a woman, Beth, who is concerned
that she may carry a variant of either the BRCA1 or BRCA2 gene that
predisposes people to breast cancer. The case study is presented in five
segments during which Beth makes two key decisions: (1) to proceed with
being tested for altered forms of these genes and (2) after she develops
cancer in one breast, not to have a prophylactic mastectomy of the other
breast. Students analyze each segment by discussing a set of questions
related to the underlying science and to the ethical and policy dilemmas
raised by the decisions.
108
Web-Based Activities In Advance
Steps 2 and 3.
Follow the instructions on page 110 to get to the Web site on the computers
students will use. If you do not have enough computers with Internet
access, you can use the print-based alternative (on pages 110 and 111).
1. Open the lesson by asking students whether they know anyone who
has had breast cancer. Invite those students who wish to briefly
describe their relationship to that person to do so.
109
Student Lesson 5
Human Genetic Variation
2. Give each student one copy of Master 5.1, Making Decisions in the Face
of Uncertainty. Direct students to organize into their small groups
and to select students to read the parts of the various characters.
Ask students simply to read the script all the way through so they
can get a sense of the complete case.
3. Give each student one copy of Master 5.2, Analyzing the Issues, and
one copy of Master 5.3, Reference Database, and explain that now
the class will read the script again, one segment at a time. Suggest
that students take notes and list questions that occur to them as they
read each segment, then respond to the related questions on Master
5.2. Discuss each segment in turn, as students complete it, using the
questions on Master 5.2 as a guide. Address any other questions the
students raise as well.
If students raise questions about the science, legal, or policy issues that
you and they cannot answer with the materials provided, suggest that
someone pursue those answers outside of class.
Beth has to decide whether to have the test for mutations in her BRCA1
and BRCA2 genes. Your students might be interested in the financial
aspects of the test. As of 2010, when this module was reprinted, the
laboratory cost for the combined test for BRCA1 and BRCA2 ranged from
several hundred to several thousand dollars. There would be additional
110
costs for the associated genetic counseling. Insurance coverage varies
depending on the company.
Beth, her husband, her mother, her sisters, her teenage daughter, and
her daughter’s future partner (if she has one).
Beth may not want to know. She also will not have to worry about
whether she should share potentially positive test results with other
members of the family. She will not have to make tough decisions
about detection and/or prevention options (for example, prophylactic
mastectomy), none of which is 100 percent effective.
Question 5. What factors do you think Beth and Charlie should consider
in making their decisions?
Question 1. What new facts have you learned about breast cancer?
Question 2. What are some of the family issues that arise in this
counseling session?
Beth’s mother feels guilty about her breast cancer and about the
possibility that she has passed on the associated mutation. The issue of
blame also arises, as well as the question of what Beth will do with the
information if the test is positive. Note that the counselor stresses the
importance of privacy and confidentiality. Emphasize for your students
that genetic counselors are trained to handle the social and emotional
aspects of counseling as well as the scientific aspects.
Question 3. What reasons does the genetic counselor give for not testing
Jennifer? Do you agree that children under 18 should not be tested?
112
• Do the benefits outweigh the harm brought about by knowledge of
the test results?
The issue becomes even more complex when the patient to be tested
is a minor, that is, under 18 years of age. The request for a genetic
test may come from the parents or from the minor. When the minor
is an adolescent, the issue becomes particularly complicated because
the patient may exhibit a considerable degree of autonomy regarding
his or her healthcare decisions. Experts agree that in these cases the
primary goal of genetic testing should be to promote the child’s well-
being. For example, the child who tests positive may be overindulged
or may be treated as a scapegoat. Both of these problems can occur,
however, even in the absence of testing. The testing of a child (or indeed
any other family member) also has implications for all members of the
family. In some cases, this forewarning will be welcomed; in others, it
may be unwanted. Genetic testing of a child will ease some aspects of
uncertainty, but people differ greatly in their response to such news.
In the case of genetic testing for mutations in the BRCA1 gene, most
healthcare providers and genetic-testing centers adhere to a policy that
denies tests to minors. This denial extends to requests from the parents,
who are the legal guardians of the child’s health. The psychological
effects can be mixed. Whereas some individuals prefer the release from
uncertainty, others could view a positive result as a death sentence
and react in ways that are destructive to themselves or their families.
Genetic testing requires informed consent, and some geneticists
argue that this requirement automatically rules out children, and
even teenagers, who generally are judged incapable of providing such
consent. This view of minors, however, may be far too broad and may
not be realistic. Some specialists are beginning to recognize that some
adolescents and young children have sufficient autonomy in consent
and decision making to make such decisions, and recommend that the
desires of these youths should be taken into account. In any event, one
must weigh the balance of potential harm and benefit in reaching a
decision about testing a minor.
One outcome of the current policy is to delay the decision to test until
the individual is an adult and can make the decision, rather than letting
parents remove this option by making the choice themselves. Note that
a change in policy most likely would result in parents being permitted
to make the decision, rather than leaving the decision to the minor in
question. Either way, issues of ethical decision making will arise.
Question 4. Beth’s mother says, “I’m not sure more information is better.”
Do you agree with her? Explain your answer.
113
Student Lesson 5
Human Genetic Variation
Question 1. Beth and her mother have had the genetic test. What new
information have we learned?
Beth and her mother are positive for the BRCA1 mutation. Beth has a
lifetime risk of perhaps about 60 percent of developing breast cancer.
This number is down from original estimates, which were as high as
90 percent. Some recent data suggest a risk figure even lower than
60 percent. In fact, as is often true when a new medical test becomes
available, the exact figure is still unknown. Further, it appears that the
risk figure may vary, depending upon the particular mutation in the
BRCA1 gene that an individual woman carries.
Students have also learned that Beth may not develop breast cancer even
though her test was positive and that Beth can do a number of things
(breast self-examinations and mammograms, for example) to help
detect any cancer early and, therefore, to begin early treatment.
Remember to emphasize that Beth and her mother were tested for
mutations in the BRCA1 and BRCA2 genes, not for cancer.
It is now three years after the genetic test, and Beth has been
diagnosed with cancer in one breast. There is a high risk of cancer
in the other breast.
First, they discuss whether Beth should have both breasts removed,
and second, they consider whether to tell Jennifer that she is at risk for
the BRCA1 mutation. Note that even removal of both breasts does not
guarantee that the cancer will not appear elsewhere or even appear in
the remaining breast tissue.
Question 3. What do you think Beth and Charlie should do? Why?
Answers will vary, but make certain that students provide sound
explanations for their positions. Again, make sure that the science
is correct.
114
Segment 5: Jennifer’s Decision
Beth has had a lumpectomy, and Jennifer has not been tested.
Emphasize that the chance of survival increases with early diagnosis.
Answers will vary. Inform students that at present many states have
laws that prohibit health insurers from accessing and using genetic
information in a discriminatory way. In addition, the federal Health
Insurance Portability and Accountability Act (HIPAA) prohibits those
who issue commercial, employer-based, group health plans from
discriminating against individuals on the basis of information gained
from genetic tests.
Fifty years ago, Beth and Jennifer would not have been faced with
the decision about whether to have these genetic tests. They most
likely would have undergone a radical mastectomy if cancer was
discovered. Our increased knowledge of human genetic variation
115
Student Lesson 5
Human Genetic Variation
Insist that students apply • How does this lesson illustrate the old saying that knowledge plus
the saying to this lesson. choice equals power?
Then, to close the module
effectively, ask students to The more we learn about a given situation—for example, our status
with respect to the BRCA1 and BRCA2 genes—the greater our
apply the saying to our
ability is to make decisions and control our own destiny, so long
growing knowledge of as the choices are available. The importance of choices emerges in
human genetic variation this lesson in at least two ways. First, Beth and Jennifer must be
(in general). Students confident that information that results from the test will not be
should see that this used against them. Otherwise they may feel, as Jennifer does, that
knowledge offers us new they are not really free to chose whether to have the test. Second,
opportunities and choices, the general policy not to test children under 18 for mutations in the
BRCA1 or BRCA2 genes has restricted the choices for people under
but it also brings new
18. This limits their access to knowledge about themselves and
challenges. restricts their power to make decisions about their own lives.
Potential Extend this lesson by challenging students to connect what they learned
in Lesson 5 with what they learned in the two preceding lessons. For
Extensions example, ask students to connect Lesson 5 with Lesson 3 by suggesting
how discovering mutations that predispose people to the development of
cancer might help scientists develop new approaches to treating cancer.
Then, assign students to learn more about this question by reading the
article “Mapping the Cancer Genome,” by F.S. Collins and A.D. Barker, in
the March 2007 Scientific American, or “Making Headway Against Cancer,”
by J. Rennie and R. Rusting, in the September 1996 special edition of
Scientific American.
116
Lesson 5 Organizer: WEB VERSION
Procedure
What the Teacher Does
Reference
Ask students if they know anyone who has had breast cancer. Page 109
Invite students who wish to briefly describe their relationship Step 1
to the individual involved to do that.
Tell students to organize into their small groups. Have students Page 110
watch the online videos in “Making Decisions in the Face of Step 2
Uncertainty.”
Give each student one copy of Master 5.2. Explain that they will Page 110
watch the videos again, one segment at a time. Suggest that Step 3
students take notes and list questions that arise.
Ask students to respond to the questions on Master 5.2 after they Page 110
watch each segment. Discuss each segment, their answers to the Step 3
questions, and any other questions students have.
Challenge students to identify the questions that now face Jennifer Page 115
about her own health and personal welfare. Invite neighboring Step 4
groups to discuss the questions.
Use the following questions to stimulate a final class discussion:
• How might Beth’s and Jennifer’s decisions have been different
50 years ago?
• What advantages does our knowledge of human genetic
variation bring us?
• What questions does it also raise?
• How does this lesson illustrate the old saying that knowledge
plus choice equals power?
117
Student Lesson 5
Human Genetic Variation
118
Masters
Lesson 1, Alike, But Not the Same
Master 1.1, An Inventory of a Few Human Traits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . student copies
Master 1.2, Thinking About Human Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . student copies
119
An Inventory of a Few Human Traits
How similar are you and your partner? Complete this inventory and compare it with your partner’s.
8. hair color: black ________ dark brown ________ light brown ________
blond ________ red ________ other ________
13. height: ________ centimeters (calculate by multiplying the height in inches × 2.5;
round off to the nearest 5 centimeters)
Master 1.1
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Thinking about Human Variation
1. Some human traits can be changed by human intervention and some cannot. Provide examples of each
of these types of traits.
2. You probably already know that some traits are genetic and others are environmental. But most human
traits reflect an interaction between genetic and environmental factors. Name some traits that might
fall into this category and explain why you think they do.
3. Describe some of the benefits of human genetic variation. What are some of the potential problems that
it can cause?
Master 1.2
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
How Much Variation?
This page contains the DNA base sequence for part of a gene called beta globin. Hemoglobin, the oxygen
carrier in blood, is composed of four polypeptide chains, two alpha polypeptide chains, and two beta
polypeptide chains. The beta globin gene encodes the amino acid sequence for the beta chain. The
complete gene is about 1,700 DNA bases long.
Master 2.1
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
How Much Variation?
This page contains the DNA base sequence for part of a gene called beta globin. Hemoglobin, the oxygen
carrier in blood, is composed of four polypeptide chains, two alpha polypeptide chains, and two beta
polypeptide chains. The beta globin gene encodes the amino acid sequence for the beta chain. The
complete gene is about 1,700 DNA bases long.
Master 2.2
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
How Much Variation?
Doing the Math
Calculate the amount of variation in the DNA in the beta globin gene between person A and person B.
If you need help, use the example below as a guide.
1. How many bases are different between the sequence shown for person A and the sequence shown for
person B? _______
How many total bases are in the sequence? _______ (Your teacher will give you this number.)
Divide the number of different bases by the total number of bases in the sequence.
3. The human genome has about 3 billion bases. Assume that the degree of difference you just calculated
applies across the entire genome. How many total base differences would you expect to find between
person A and person B?
Example
The sophomore class at Roosevelt High School in Metropolitan City is one of five high schools that conduct two
community service projects each year, one in the fall and one in the spring. This fall, 150 students from Roosevelt High
signed up to help. The same number signed up in the spring, but 30 of the students were different. What percentage of
the students was different between the fall group and the spring group?
1. To calculate the percentage difference, first divide the number of different students in the spring by the total
number of students in the group:
3. The sophomore classes at all five high schools combined include about 3,000 students. Assume that the degree
of difference between the students who signed up for the community service projects in the fall and spring
across all five high schools is the same as it was at Roosevelt High. How many different students would you
expect to find in total between the fall and spring projects?
Master 2.3
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Exploring Sickle Cell Disease
Imagine that you are a family-practice physician and that an African American woman, Audrey Lindsey,
and her family are your patients. Just before her twins, Sondra and Jason, were born, Ms. Lindsey’s
husband, also African American, died in an automobile accident. His parents were physiologically normal,
but he had a brother who died of sickle cell disease at the age of 19. Ms. Lindsey explains to you that it is
important to her to know whether her twins carry the allele associated with sickle cell disease.
1. Depending on whether or not you have access to the Internet, use either the online documentary
“What Is Sickle Cell Disease?” and Sickle Cell Database or Master 2.5, Reference Database: Sickle Cell
Disease—and any other resources that are available to you (for example, your textbook)—to answer
the following questions:
a. What are the primary symptoms of sickle cell disease? What happens in a person’s body to cause
these symptoms?
d. What does this difference in hemoglobin tell you about the DNA of people whose cells make Hb S as
compared with people whose cells make Hb A?
e. What is the difference between sickle cell disease and sickle cell trait? Demonstrate in your answer
that you understand how sickle cell disease is inherited.
2. Use what you learned about sickle cell disease and trait to propose a way to determine whether
Ms. Lindsey’s twins have sickle cell trait. Explain your procedure to your teacher, then use the
information provided on the handout your teacher will give you to determine the results of the test.
3. Write the dialogue for a brief scene (2–3 minutes) in which you explain to Ms. Lindsey the results of
the tests you ran on the twins, what these results say about the inheritance of the sickle cell trait in
her family, and the implications of your findings for the twins’ health.
Master 2.4
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Reference Database
Sickle cell disease is a genetic disorder that affects approximately 1 out of every 625 African Americans in
the United States. It is caused by a single amino acid change in a protein called hemoglobin.
Hemoglobin is the major protein inside red blood cells. Its primary function is to transport oxygen. When
the oxygen concentration in the blood decreases, the defective hemoglobin molecule forms long crystals
inside the red blood cell. These crystals cause the red blood cells to elongate and assume a “sickle” shape.
The crystallized hemoglobin also damages the cell membrane so that the cells become very fragile.
In some parts of Africa, about 4 percent of black Africans have sickle cell disease.
Why does sickle cell disease occur more frequently among black Africans than among African
Americans? Scientists believe that this difference is related to the threat of a fatal form of malaria that
occurs in many parts of Africa. Studies reveal that people who are homozygous for the normal allele
for hemoglobin (Hb A/Hb A) often die of malaria. However, people with sickle cell trait (people who are
heterozygous, Hb A/Hb S) do not contract the fatal form of malaria. Thus, more heterozygotes live than
do people who are homozygous for the normal allele, and these people often pass the sickle cell allele on
to their children. This phenomenon keeps the incidence of the sickle cell allele in the population higher
than it would be if there were no threat of malaria.
About one-quarter of 1 percent (0.25%) of African Americans are homozygous for the sickle cell
hemoglobin allele and have sickle cell disease.
Why is the incidence of sickle cell disease in the United States so low? It is low because people with
sickle cell disease often die in childhood or early adulthood, before they have had children. Thus, many
people with sickle cell disease do not pass this allele on to children. Instead, most inheritance of the
allele is from a parent who is heterozygous for the allele to one or more of his or her children.
Sickle cell disease results when a person inherits an allele for sickle cell hemoglobin from each of his or
her parents. This inheritance pattern means that the person is homozygous for sickle cell hemoglobin and
that his or her body does not produce any normal hemoglobin, only sickle cell hemoglobin.
Geneticists show the inheritance pattern of sickle cell disease by using symbols to represent the allele
for normal hemoglobin (Hb A) and the allele for sickle cell hemoglobin (Hb S). A person with normal
hemoglobin has inherited one allele for normal hemoglobin from each parent and so has the genotype
Hb A/Hb A. In contrast, a person who has sickle cell disease has inherited one sickle cell allele from each
parent and has the genotype Hb S/Hb S.
But what about a person who inherits an allele for normal hemoglobin from one parent and an allele for
sickle cell hemoglobin from the other parent? This person has the genotype Hb A/Hb S and is said to have
sickle cell trait. Although some of the hemoglobin in this person’s body is sickle cell hemoglobin, the rest
of the hemoglobin is normal, and the person usually exhibits no symptoms of the disease.
The hemoglobin that is made in the bodies of people with sickle cell disease (Hb S) differs from normal
hemoglobin (Hb A) in just one amino acid. In normal hemoglobin, this amino acid is a glutamic acid. In
sickle cell hemoglobin, it is a valine.
People with sickle cell disease may experience symptoms such as severe pain, fever, and even death.
These symptoms occur when the misshapen red blood cells that form under conditions of low oxygen
concentration clog blood vessels and burst.
Such patients frequently experience a vicious cycle of events called a “sickle cell disease crisis” in which
low oxygen concentration causes sickling, which causes ruptured red blood cells, which in turn, causes
even lower oxygen concentrations in the body and still more sickling and red blood cell destruction. This
process leads to a serious loss of red blood cells within a few hours and can cause death.
Normal hemoglobin (Hb A) and sickle cell hemoglobin (Hb S) differ in just one amino acid. Hb S has
valine in the position where Hb A has glutamic acid. This difference results from a difference between the
DNA sequence of the allele that codes for normal hemoglobin and the sequence of the allele that codes for
sickle cell hemoglobin.
The difference in one amino acid between Hb A and Hb S causes a difference in the electrical charge of
the two forms of hemoglobin. Hb A has a greater negative charge than Hb S. This difference can be used
to distinguish Hb A and Hb S in a process called electrophoresis. Hemoglobin from individuals suspected
of having sickle cell disease or sickle cell trait is placed on a gelatinous slab (gel) beside standards of Hb
A and Hb S. An electrical charge is applied across the gel, and the proteins move through the gel toward
the positive end of the electrical field at a rate based on their size and charge. Because Hb A has a greater
negative charge than Hb S, it will move further through the gel. After electrophoresis, the gel is removed
and stained with a solution that adheres to proteins, revealing “bands” of stain at the positions to which
the hemoglobin has migrated.
Doctors diagnose sickle cell disease by comparing the banding position of hemoglobin from an individual
with the banding positions of Hb A and Hb S standards. An individual who is homozygous for Hb A will
have only one protein band on the gel, at the same position as the Hb A standard, whereas an individual
who is homozygous for Hb S (and has sickle cell disease) will also have one protein band on the gel, but
at the same position as the Hb S standard. A heterozygous individual will have two protein bands, one at
each position.
Examine the following results to determine Sondra’s and Jason’s status with respect to sickle cell trait.
1 2 3 4
Lane
1 Standard—DNA from allele for Hb A
2 DNA from Sondra Lindsey
3 DNA from Jason Lindsey
4 Standard—DNA from allele for Hb S
Master 2.6
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Molecular Medicine Comes of Age
Master 3.1
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm A, Role:
Team Coordinator
You are an experienced executive for Firm A, a U.S.-based company that develops, tests, manufactures,
and distributes pharmaceuticals worldwide. Although you worked in a research lab years ago,
your assignments have changed across the years. Now, you head up a small team of scientists and
biostatisticians.* The team provides expert advice to the much larger teams that actually design,
develop, and test new drugs.
You receive an e-mail from Firm A’s vice president for research. The e-mail asks your team to evaluate
a problem the company is having with one of the drugs it is developing. Because of the importance of
this drug to the company’s future, you decide to call a team meeting for the next day. To prepare for the
meeting, you study the relevant section of the e-mail closely.
What’s going on here? Can you find a pattern in the data that will
help us understand how the drug is acting? To make this drug
marketable, we need to define exactly when or with whom the drug
is likely to be effective. If we can’t, physicians will have no reason to
prescribe it over another drug.
* A biostatistician is trained in biology and statistical analysis. Biostatisticians are experts in the experimental designs and statistical
methods that are most helpful in conducting research in biology and medicine.
Master 3.2
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm A, Role:
Physiologist
You are an experienced physiologist* for Firm A, a U.S.-based company that develops, tests,
manufactures, and distributes pharmaceuticals worldwide. You are part of a small team of scientists and
biostatisticians.** The team provides expert advice to the much larger teams that actually design, develop,
and test new drugs.
You have been reading a research report in your office. Now, your assistant calls to say that the leader
of your team has called a special team meeting to evaluate a problem the company is having with one of
the drugs it is developing. Because of the importance of this drug to the company’s future, you are not
surprised your team leader has called this meeting. You don’t know much about the condition the drug is
intended to treat. You pull out a medical textbook to learn more about it.
Asthma
* A physiologist studies the basic processes of life, such as respiration, digestion, circulation, and cellular metabolism.
** A biostatistician is trained in biology and statistical analysis. Biostatisticians are experts in the experimental designs and statistical
methods that are most helpful in conducting research in biology and medicine.
Master 3.3
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm A, Role:
Molecular Biologist
You are an experienced molecular biologist* who works for Firm A, a U.S.-based company that develops,
tests, manufactures, and distributes pharmaceuticals worldwide. You are part of a small team of scientists
and biostatisticians.** The team provides expert advice to the much larger teams that actually design,
develop, and test new drugs.
Your assistant has left you a note. It says that the leader of your team has called a special team meeting
to evaluate a problem the company is having with one of the drugs it is developing. Because of the
importance of this drug to the company’s future, you are not surprised that your team leader is taking
this problem so seriously. You pick up a scientific article and decide to spend the rest of the afternoon
studying it.
The article includes a table showing the response to the drug based on the patients’ genotype:
Genotype, Based
on ApoE Type None Low Moderate High
1
E2/E2 X
E3/E32 X
1
E4/E4 X
1
These genotypes are uncommon.
2
This genotype is common.
* A molecular biologist studies the structures and processes of life at the molecular level. Molecular biologists investigate such
things as the structure of proteins and DNA and how these molecules regulate cellular activities.
** A biostatistician is trained in biology and statistical analysis. Biostatisticians are experts in the experimental designs and statistical
methods that are most helpful in conducting research in biology and medicine.
Master 3.4
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm A, Role:
Biostatistician
You are an experienced biostatistician* who works for Firm A, a U.S.-based company that develops, tests,
manufactures, and distributes pharmaceuticals worldwide. You are part of a small team of scientists and
biostatisticians. The team provides expert advice to the much larger teams that actually design, develop,
and test new drugs.
You have been analyzing a new set of test results that one of those larger teams just sent you. Now, your
assistant comes into your office to say that the leader of your team has called a special team meeting. The
objective is to evaluate a problem the company is having with one of the drugs it is developing. Because
of the importance of this drug to the company’s future, you are not surprised that your team leader is
taking this problem so seriously. You decide you’d better learn something about the problem before the
meeting. Using the company’s database, you call up the test results on the drug and study them carefully.
CONFIDENTIAL
Do not discuss or circulate
these data outside Firm A.
Table 1. Effect of Drug X on Wheezing Associated with Asthma in 300 Children (Preliminary Results)
1. Calculate the percentages by dividing the number of children in each row by the total number of
children (300). Record the percentages where indicated in the table.
3. Could it be related to the sex of the child? Could it be related to whether the child has a pet.
* A biostatistician is trained in biology and statistical analysis. Biostatisticians are experts in the experimental designs and statistical
methods that are most helpful in conducting research in biology and medicine.
1. Calculate the percentages by dividing the number of children in each cell by the total number of
children (154 for girls; 146 for boys).
2. Based on the data above, does sex explain why some children experience no relief from symptoms of
asthma after using Drug X? Why or why not?
Table 3. Effect of Exposure to Pet Dander* on Response to Drug X among 300 Children
* Pet dander is tiny particles of hair, skin, or feathers that can cause an allergic reaction like asthma.
1. Calculate the percentages by dividing the number of children in each cell by the total number of
children (120 for those with pets; 180 for those without pets).
2. Based on the data above, does exposure to pet dander explain why some children experience no relief
from symptoms of asthma after using Drug X? Why or why not?
Use this form to organize your discussion about Drug X and report your team’s results. You and your
teammates will have 30 minutes to complete this form. Be prepared to explain your analysis and
proposed solution to the rest of the class.
2. Describe asthma in your own words (refer to the Team Coordinator and Physiologist handouts).
3. What is Drug X designed to do for asthma sufferers (refer to the Team Coordinator and Physiologist
handouts)?
4. Look at the preliminary test results (refer to the Biostatistician handout). Can you predict which group
will be helped most or least by Drug X? For example, does the sex of an individual make a difference?
Does having pets make a difference? Explain your answers.
5. What does the example of ApoE (refer to the Molecular Biologist handout) suggest might be happening
with Drug X? Based on this example, what might Firm A investigate?
6. Firm A’s vice president for research (your teacher) will provide you with some new data. What do the
new data reveal about Drug X?
8. Has your team solved the biological problem facing the company with respect to Drug X? What new
problems has it raised?
Master 3.6
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Some New Genetic Data about Firm A
CONFIDENTIAL
Do not discuss or circulate
these data outside Firm A.
Master 3.7
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm B, Role:
Team Coordinator
You are an experienced executive for Firm B, a U.S.-based company that develops, tests, manufactures,
and distributes pharmaceuticals worldwide. Although you worked in a research lab years ago, your
assignments have changed across the years. Now, you head up a small team of scientists that provides
expert advice to the much larger teams that actually design, develop, and test new drugs.
You receive an e-mail from Firm B’s vice president for research with a new assignment for your team.
Although one of the company’s major products is still doing very well in the marketplace, the vice
president wants to be sure that the company keeps its competitive edge in this area. Because of the
importance of this product to the company’s well-being, you decide to call a team meeting for the next
day. To prepare for the meeting, you study the relevant section of the e-mail closely.
Master 3.8
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm B, Role:
Physiologist
You are an experienced physiologist* for Firm B, a U.S.-based company that develops, tests, manufactures,
and distributes pharmaceuticals worldwide. You are part of a small team of scientists that provides expert
advice to the much larger teams that actually design, develop, and test new drugs.
You have been reading a research report in your office. Now, your assistant calls to say that the leader
of your team has called a special team meeting to do some brainstorming about new approaches the
company could take in developing drugs for the treatment of cystic fibrosis. You know that Drug Y, your
company’s major product, is widely used as a treatment for this disease. Still, a lot has been learned about
cystic fibrosis in the last few years. If the company is to maintain its competitive edge, it needs to keep
looking for new, more effective treatments. You don’t know much about cystic fibrosis, so you pull out a
medical textbook to learn more about it.
Cystic Fibrosis
* A physiologist studies the basic processes of life, such as respiration, digestion, circulation, or cellular metabolism.
Master 3.9
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm B, Role:
Molecular Biologist
You are an experienced molecular biologist* for Firm B, a U.S.-based company that develops, tests,
manufactures, and distributes pharmaceuticals worldwide. You are part of a small team of scientists that
provides expert advice to the much larger teams that actually design, develop, and test new drugs.
Your assistant has left you a note. It says that the leader of your team has called a special team meeting
to do some brainstorming about new approaches the company could take in developing drugs for the
treatment of cystic fibrosis. You know that Drug Y, your company’s major product, is widely used as
a treatment for this disease. Still, if the company is to maintain its competitive edge, it needs to keep
looking for new, more effective treatments. You decide to find out what the latest research says about CF,
and you pick up a recent article.
As you read, you develop a flow chart of the biological effects of the most common CF mutation:
1. A person inherits two mutated genes for the CFTR protein.
Ð
2. These mutations result in one missing amino acid in the CFTR protein that his or her cells make.
Ð
3. The absence of this amino acid means that the CFTR protein in his or her cells does not fold
into its proper shape.
Ð
4. Most of this improperly folded CFTR protein is destroyed before it can be inserted into
the cell membrane.
Ð
5. The absence of properly functioning CFTR protein in the cell membrane leads to
abnormal movement of chloride ions and water in and out of the cell.
Ð
6. The result of this abnormal movement of chloride ions and water is the
production of thick, sticky mucus.
* A molecular biologist studies the structure and processes of life at the molecular level. Molecular biologists are interested in
such things as the structure and function of proteins and DNA and the molecular mechanisms that regulate activities inside
the cell.
Master 3.10
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Saving Firm B, Role:
Physician
You are an experienced physician for Firm B, a U.S.-based company that develops, tests, manufactures,
and distributes pharmaceuticals worldwide. You are part of a small team of scientists that provides expert
advice to the much larger teams that actually design, develop, and test new drugs.
You have been analyzing a new set of test results that one of those larger teams just sent you. Now, your
assistant comes into your office to say that the leader of your team has called a special team meeting
to do some brainstorming about new approaches the company could take in developing drugs for the
treatment of cystic fibrosis (CF). You know that Drug Y, your company’s major product, is widely used as
a treatment for this disease. Still, a lot has been learned about CF in the last few years. If the company is
to maintain its competitive edge, it needs to keep looking for new, more effective treatments. You decide
that you will prepare for the meeting by learning more about Drug Y and also by learning about other
companies’ products to treat CF. You pull out some reference material and learn that improvements in
treatment across the past few years have increased the average survival time of patients with CF from
under 5 years to approximately 30 years. You create a table to help you organize what you learn about
these treatments, but leave the last column blank in order to discuss it with your teammates.
Treatment Addresses
Major Type Description Primary Benefit Symptoms or Cause?
chest physical therapy vigorous tapping on dislodges mucus from
the back and chest with lungs, allowing better
cupped hands breathing and reducing
the risk of infection
antibiotics antibiotics administered treats lung infections
intravenously, through that can damage the
pills, or, in the case of lungs and even cause
Drug Y, as a medicated death
vapor that is inhaled
enzyme supplements supplements of improves digestion
pancreatic enzymes
diet enriched diet and reduces malnutrition
supplements of vitamins and improves growth
and other nutrients and development
Master 3.11
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Report Form for Firm B
Use this form to organize your discussion about Drug Y and report your team’s results. You and your
teammates will have 30 minutes to complete this form. Be prepared to explain your analysis and
proposed solution to the rest of the class.
1. What is the problem facing Firm B with respect to Drug Y (refer to the Team Coordinator handout,
Master 3.8)?
2. Describe cystic fibrosis (CF) in your own words (refer to the Physiologist handout, Master 3.9).
3. What have we learned in the past few years about the cause of CF (refer to the Molecular Biologist
handout, Master 3.10)?
4. What is Drug Y (and most other current treatments) designed to do for CF patients (refer to the
Physician handout, Master 3.11, and discuss what goes in the last column of the table provided)?
5. Firm B’s vice president for research (your teacher) will provide you with some new information. What
clue does this new information provide about how Firm B might approach developing new treatments
for CF?
6. What new approaches do you recommend Firm B consider as it attempts to design and develop one or
more new treatments for CF?
7. Has your team solved the problem facing the company with respect to Drug Y? What new problems
has it raised?
Master 3.12
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Some New Information about Firm B
INTEROFFICE MEMO
TO: Team Investigating New Treatment Approaches for Cystic Fibrosis
FROM: Vice President for Research, Firm B
CONFIDENTIAL
Do not discuss or circulate
this memo outside Firm B.
I just heard from a colleague that another research team (not associated with our company)
will apply soon for a patent on a new method for treating cystic fibrosis. These researchers have
spent years studying exactly what goes wrong in CF cells. The new method they will propose
involves using small fragments of a protein normally found in brain cells to create working
chloride channels in CF cells that lack such channels. Does this offer us any clues about how
we might change our treatment approach to CF? Are there any other places in the flow chart of
biological effects of CF where we could intervene to correct the problems in CF cells?
Master 3.13
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Rolling the Dice
Imagine that you are going to live your entire life—your teen years, your adult years, and your senior-
citizen years—in the next 10 minutes and that your choices in life are going to be made by a roll of the
dice. Begin with your teen years and roll one die to discover your behavioral choices in each category
for each life stage. Use the information provided to determine how many points you receive for each
behavior. Record the result in the blanks provided.
By the way, the object of this game is to stay alive to a ripe old age. You do this by keeping your “heart
points” below the threshold level of 85. Once you exceed 85 points at any life stage, you’re out (you’ve had
a fatal heart attack).
If the total is more than 85, you’ve had a fatal heart attack.
3 or 4 You smoked during your teen years, but you have stopped smoking*
(subtract 20 points). ________
You did not smoke during your teen years (subtract 5 points). ________
5 or 6 You smoke one or more packs of cigarettes a day (add 20 points). ________
If the total is more than 85, you’ve had a fatal heart attack.
If the total is more than 85, you’ve had a fatal heart attack.
Complete the following steps to compare the results of the game with and without considering
genetic factors.
1. Transfer your heart points from Rolling the Dice into the left-hand column below.
2. Your relevant genes envelope contained heart points related to your genetic risk. Enter that number in
the right-hand column below and recalculate your total points for each life stage.
Review—Risk from Behavioral Choices Only Recalculate—Risk from Genes and Choices
Relevant genes _______
Life Stage 1: Teen years _______ Life Stage 1: Teen years + _______
Subtotal _______
Life Stage 2: Adult years + _______ Life Stage 2: Adult years + _______
Subtotal _______ Subtotal _______
Life Stage 3: Senior-citizen years + _______ Life Stage 3: Senior-citizen years + _______
Total _______ Total _______
3. Remember, if you exceeded 85 points in any life stage, you have had a fatal heart attack. What effect
did including your points for genetic risk have on your outcome?
4. Think about the behavioral choices you made in each life stage.
6. Assume that genetic testing showed that you were at increased risk for a fatal heart attack 20 years
from now. Would you want to know? Why or why not? Would that information cause you to change
your behavior? If not, what kind of information or event would cause you to change your behavior?
7. We know about only a few genes that affect the likelihood of a heart attack, and we have the ability to
test for even fewer of them. In the future, we certainly will learn about more of these genes. How will
an increased knowledge of the genetic factors associated with heart disease have a positive impact on
individuals and society? How will it have a negative impact?
8. Our ability to detect genetic variations that are related to common diseases likely will improve. How
might that ability shift some of the responsibility for health care from physicians to individuals?
Master 4.3
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Moderate Genetic Risk
Master 4.4
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Low Genetic Risk
Master 4.5
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Genetic Protection
Genetic Protection
Genetic Protection
Genetic Protection
Genetic Protection
Master 4.6
Copyright © 1999 by BSCS and Videodiscovery, Inc. Permission granted for classroom use. Updated 2011.
Making Decisions in the Face of Uncertainty
Characters Beth
Charlie, Beth’s husband
Genetic Counselor (GC)
Mother, Beth’s mother
Jennifer, Beth’s daughter
Beth: I just read a newspaper article about a test for a breast cancer gene. I guess with Mom’s
diagnosis, I’m worrying about it.
Beth: When mom was first diagnosed with cancer when she was my age. I remember it, I was
13 years old. It wasn’t easy. And I never told you my grandmother died from ovarian cancer.
Beth: Apparently there is a special kind of cancer that runs in families. If you have a certain
form of this gene, you’re at a high risk of getting breast cancer. Now they have a test for
it.
Beth: I don’t know. At least you know that you’re more susceptible. Or you find out that
you’re safe.
Charlie: (Kindly) So go get the test if it’ll put your mind at ease.
Beth: But that’s just it. I don’t know if it would make me feel safer. What if I find out that I do
have it? I’ll feel doomed.
Charlie: I think we should find out. As soon as possible. You’ve got a cloud hanging over you as
it is.
Beth: A cloud! Do you know how worried I’ve been all these years? That’s why I was so
confused about taking birth control pills. At first, they thought it would increase the
risk of getting breast cancer, so I didn’t take them. Now, I read that it can actually lower
the risk of ovarian cancer.
Charlie: Wouldn’t you feel better if you knew for sure about that gene?
GC: I’d like to make sure we all understand what we are here to discuss.
GC: Beth is interested in having the BRCA1 and 2 genetic tests. These tests help us identify
women who have a genetic predisposition toward breast cancer and we find that we
can get more information to help us understand Beth’s situation if we first test family
members who already have cancer.
Mother: I’ve already been through the ringer with this disease. What possible good is this test
going to do for me?
Beth: This test is for me mother. I have a right to know . . . And for the sake of my family.
Mother: I’m already the family outcast, the one with this condition, who has passed it on to all
of you.
Beth: No one is blaming you mother. This is just something our family has to deal with.
GC: Let’s not get ahead of ourselves. The first step is to understand what such a test can tell
you and then decide if this is information that you want to know.
Mother: What if the family doesn’t want to deal with it. Your sisters, aunts and cousins might
not want to know all this stuff. It’ll be one more thing to have a big family ruckus over.
GC: You will decide who you want to tell. Now we will encourage you to tell your relatives
because the information can be useful to them regardless of the result. I can help you
think about how to tell them if you decide you want to.
Mother: And if I take the test and it turns out that my cancer was related to one of these
mutations, what will you do?
Beth: Well, I’d continue to watch carefully for any signs of cancer, and I’d get Jennifer tested.
She’s my teenage daughter.
GC: I can understand your concern about your daughter. But there are several reasons why
we do not offer testing to children under 18 years of age. The foremost being, that the
test results won’t change the care we give Jennifer.
Mother: The world has gotten so complicated. I don’t know that more information is better. But
you are right, I should get tested so that you can have a better idea of what to do. My
sister has been wondering if she’s at risk as well. After everything I’ve been through, I’ll
be able to handle this information.
Beth: I really appreciate this mom. I want to know. I’ll either be relieved, or I’ll have
something real to worry about.
GC: Beth, the tests show that you and your mother have the BRCA1 mutation.
Beth: Hmm. I had a feeling about this after my mother’s test was positive. So what does this
mean for my family and me?
GC: Two things. For your family, it means that you could pass this mutation to your children.
For your own health, it means you have an increased risk of developing breast and ovarian
cancer and possibly at a younger age.
GC: You can continue to watch yourself closely and get regular checkups. We might want you
to start having mammograms earlier than you normally would. If you do develop cancer,
early detection greatly improves your chances that the treatment will be effective. In
addition, some people consider preventive surgery, but that is a tougher decision to make.
Beth: I see. I know my sister is going to want to get tested. If her results are negative does that
mean she is safe?
GC: If she doesn’t have the mutation then she probably has about the same risk of developing
breast cancer as other women without the mutation.
GC: Your son and daughter each have a 50 percent chance of having the mutation we see
in your family. You probably will want to think about whether you want to share this
information with them. Nothing at this time indicates that we would change their medical
care in any way.
Beth: You’re right. I need to think about all of this for a while. Jennifer would probably want to
know. But my son is only 12. It might cause him to worry rather than help him.
GC: Take your time adjusting to this news. We can meet again to discuss how you’re doing and
what you want to tell your children. Do you have any concerns?
Beth: It’s just that now I feel so different from other people.
GC: Everyone is different. Just as people vary in their physical appearance, they also vary
in their susceptibility to disease. What you are feeling is perfectly normal. It may take
a while for you to accept it. Give yourself some time. Talking with some of your family
members, even your mother, may help.
Beth: At least now I know some of the cards I’ve been dealt.
Charlie: I felt the oncologist was encouraging. It’s really good that we caught it early.
Beth: Ever since Mom got her results, I knew I was going to have the mutation too. I knew
this was going to happen.
Beth: Yeah, just chance . . . It was a relief that Aunt Susan tested negative for both genes.
At least my cousins don’t have to worry. And now that I know that I have cancer, I’m
actually a little relieved.
Charlie: Relieved?
Beth: Now I can focus on something specific. You know, I’d been thinking about having both
my breasts removed, even before the cancer. Now I have a real reason to do it.
Charlie: Beth, you’ve got to stay positive. Medicine is getting better. They have a whole treatment
plan worked out for you. They said there wasn’t any trace of cancer in your other breast.
Beth: You know, we probably should tell her about my positive gene test too. I know we felt
that she was too young when I got tested, but maybe now maybe she really should get
the test.
Charlie: She’s barely 19, she’s doing so well in college. This is going to be a lot for her to handle
all at once.
Charlie: She’s still young. We’ve got some breathing room. Let’s just take things one step at a
time.
Beth: Yeah, I feel good. I didn’t know it would take so long for my energy to come back.
Beth: Thanks. It’s been a year since the lumpectomy and so far it looks like I’ve been cured.
How about you? Have you given any more thought to the test?
Jennifer: Sure, I think about it. I’m young and I live my life like I’m at a high risk anyway.
Jennifer: Of course, once a month. And I go to the doctor twice a year. The nurses even know the
name of my cat.
Beth: We were so worried about how you’d handle all this information.
Jennifer: Well, now I’m more worried about what other people know about me.
Beth: They can’t ask you about personal stuff, can they?
Jennifer: Maybe not, but after I’m hired I want to make sure that I get my health insurance. I
don’t want to go in with this test on my record.
Jennifer: For the insurance companies, it’s just business. Anyway, I just don’t need to know about
this gene, at least not now.
Beth: It’s up to you, but I can’t help still being your mother.
Use this worksheet to take notes while you either watch the video Making Decisions in the Face of
Uncertainty a second time or reread the dialogue on Master 5.1, segment by segment. List any questions
that occur to you. Be prepared to discuss these questions at the time your teacher indicates.
5. What factors do you think Beth and Charlie should consider in making their decisions?
2. What are some of the family issues that arise in this counseling session?
3. What reasons does the genetic counselor give for not testing Jennifer? Do you agree that children under
18 should not be tested?
1. Beth and her mother have had the genetic test. What new information have we learned?
2. What major decisions do Beth and her husband discuss in this segment?
3. Do you think employers or insurers should be able to deny employment or insurance to a person who
has a genetic predisposition to a disease such as cancer? Explain your position.
Breast Cancer—Causes
A person’s cells contain a variety of genes that normally work together to control cell division so that
more cells are produced only when the body needs them. The transformation of a cell from normal
to cancerous requires that the cell experience several separate changes (mutations) in the genes that
control division. When such changes occur in breast or other tissue, cells keep dividing even when
new cells are not needed, and a tumor may form.
Breast Cancer—Definition
Cancer is a group of more than 100 diseases that occur when cells become abnormal and divide
without control or order. This abnormal division may produce a tumor that can be benign (not
cancerous) or malignant (cancerous). Malignant tumors can invade, damage, and destroy nearby
tissues and spread to other parts of the body.
There are several types of breast cancer. The most common begins in the lining of the milk ducts of
the breast. Another type begins in the lobules where milk is produced. If a malignant tumor invades
nearby tissues (for example, lymph nodes in the area), it is known as invasive cancer.
Breast Cancer—Detection
The earliest sign of breast cancer is usually an abnormality that shows up on a mammogram (a
special X-ray of the breast) before it can be felt by the woman or a healthcare provider. When breast
cancer has developed to the point where physical signs and symptoms exist, these symptoms may
include a lump, thickening, swelling, distortion, or tenderness in the breast, or skin irritation or
dimpling.
The value of mammography is that it can help healthcare workers identify breast abnormalities that
may be cancer at an early stage before physical symptoms develop. Many studies have shown that
early detection increases survival and expands treatment options.
Most breast lumps are not cancerous, but only a physician can determine this. When a woman has a
suspicious lump, or when a suspicious area is detected on a mammogram, further tests are typically
done to make a definite diagnosis.
Breast Cancer—Incidence
Breast cancer is the most frequently diagnosed nonskin cancer and the second most common cause
of death for American women. Approximately 178,000 new cases of invasive breast cancer were
expected to be diagnosed in the United States in 1998. This number translates to an incidence rate of
about 110 cases per 100,000 women. About 1,600 new cases of invasive breast cancer were expected
to be diagnosed in men.
Breast Cancer—Survival
The five-year survival rate for localized breast cancer (cancer that has not spread) has increased from
72 percent in the late 1940s to more than 95 percent today.
If the cancer has spread regionally, however, the five-year survival rate is 76 percent. If it has spread
to distant sites, the rate is 21 percent.
Breast Cancer—Treatment
Depending on the medical situation and the patient’s preference, treatment may involve lumpectomy
(removal of the tumor) and removal of the lymph nodes under the arm; mastectomy (removal of the
breast) and removal of the lymph nodes under the arm; radiation therapy; chemotherapy; or hormone
therapy. Sometimes two or more treatment approaches are used in combination.
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