R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Learning Cycle Stage(s): Engage/Explore/Explain

Adapted from: Ethical, Legal, and Social Issues of Genomic Research Robert Banks, Malcolm Shabazz City High School, WI Corinne Engelman, University of Wisconsin, WI

ASHG Concept(s) Addressed: Gene expression and regulation #11; Genetics and society #20

Time Required: 100-180 minutes

Engage 1) Show this advertisement for 23andMe’s Personal Genome Service to students: http://

www.ispot.tv/ad/7qoF/23-and-me. 2) Ask students to share what they observed/heard from the video. Observations might include:

a. The connection between DNA and identity—“self portrait” b. Specific items in 23andMe data will explain certain traits c. The risk you’re going to get certain conditions d. Recommendations for follow-up, treatment, lifestyle changes to reduce risk

3) Conduct a quick poll of students. Would you pay $99 to have your DNA analyzed? For those who say yes, ask a few students what they would hope to learn.

4) Now show students the video found here (http://youtu.be/J3thpJNvA3o), which is a review from a person who had their genome analyzed by 23andMe. a. In the first minute of this video, the reviewer discusses the FDA’s cease and desist letter to

23andMe in November of 2013. More information about the letter can be found in these arti-cles: i. FDA Warning Letter to 23andMe, Inc. 11/22/13, http://www.fda.gov/ICECI/

EnforcementActions/WarningLetters/2013/ucm376296.htm ii. Wharton Business School at University of Pennsylvania article, http://

knowledge.wharton.upenn.edu/article/fda-vs-23andme-lesson-health-care-entrepreneurs/ iii. Nature Comment on FDA direct-to-consumer testing , http://www.nature.com/news/

regulation-the-fda-is-overcautious-on-consumer-genomics-1.14527 iv. New York Times article about the validity of direct-to-consumer testing, http://

www.nytimes.com/2013/12/31/science/i-had-my-dna-picture-taken-with-varying-results.html?pagewanted=all&_r=1&

v. LiveScience article about the limitations of direct-to-consumer testing, http://www.livescience.com/41534-23andme-direct-to-consumer-genetic-test-shortcomings.html

b. Ask students what additional information they heard/observed from this video. Answers might include: i. Some diseases are locked because customers may not want the information ii. Risk analysis for different traits/conditions have different scientific accuracies iii. For many of the tested traits/conditions, genes and environment play a role iv. Information on drug response, inherited conditions, traits, ancestry, etc.

5) Ask students if anyone’s answer to “Would you pay $99 to have your DNA analyzed?“ has changed. If so, why? Would you want to know ALL of your results, even for the potentially untreat-

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Lesson 2: Direct-to-Consumer Genetic Testing

R. Banks, C. Engelman, ASHG GENA 2008 Cohort

able conditions? Explore 1) Give each student a set of mock 23andMe “Spit Kit” results (Appendix I). Have students choose one

disease or trait from their report to research using the suggested online resources in Appendix II. a. For the first part of their research, have students create a FAQ sheet (Appendix III) about the dis-

ease or trait they have chosen. Note: Students that have chosen the “Resistance to HIV/AIDS” trait should create a FAQ sheet about HIV/AIDS itself.

b. For the second part of their research, have students view the 23andMe sample report (Appendix IV) for their disease/trait of interest and the marker legend (Appendix V), and answer the questions in Appendix VI. i. The sample reports are for Lilly Mendel, a fictional person. Make sure students understand

that they are using the reports for information on what markers 23andMe tests and the re-search linking each marker to the disease or trait of interest—the reported genotype and risk analysis for Lilly Mendel is irrelevant for their analysis.

ii. Sections that may be particularly helpful include the summary for each disease/trait above “Your Results,” “Understanding Your Results,” the gray bars on the “Marker Effects” chart (these show the maximum possible effect for each marker), and the “Technical Report” sum-mary for each marker.

iii. Some diseases/traits only have Established Research markers, some only have Preliminary Re-search markers, and some have both.

2) Group students who have researched the same disease/trait (no more than four students per group) and have them discuss the following question: “Given the information you have collected, how useful do you think the genetic risk assessment on your spit kit reports is for this disease/trait? Is it accurate? Is it relevant? Justify your answer using at least three criteria.” While monitoring the small group dis-cussions, prompt students to consider the completeness of the set of markers tested, the validity of the link between each marker and the disease/trait of interest, the magnitude of reported relative risk, and the overall heritability of the disease/trait.

3) Ask each group to summarize its discussion for the class. Record reoccurring themes on the board or on chart paper and save for the following lesson.

4) Ask students to return to their small groups and consider the following questions: a. Are there benefits to DTC genetic testing for your disease/trait? b. Are there drawbacks to DTC genetic testing for your disease/trait?

5) Ask each group to summarize its discussion for the class. Again, record recurring themes. Explain 1) Introduce students to the concept of genetic determinism using the opening paragraph on pg. 31 of

Chapter 3: Genetic Determinism from DNA: Promise and Peril (McCabe, Linda L. & McCabe, Edward R.B. Regents of the University of California Press, 2008.).

2) Ask students to revisit their research and offer one piece of evidence either in support of or refuting genetic determinism. Discuss briefly with a partner.

3) Have students read pgs. 44-53 of Chapter 3: Genetic Determinism from DNA: Promise and Peril by Lin-da and Edward McCabe using the reading guide in Appendix VII. Eugenics is discussed in this section and may not be a term that students are familiar with. It is

defined as “applied science or the biosocial movement which advocates the use of practices aimed at improving the genetic composition of a population. Usually refers to human popula-

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

tions.” (National Library of Medicine, http://ghr.nlm.nih.gov/glossary=eugenics).

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Appendix I Results from the 23andMe “Spit Kit” (Sample #1) Beta Thalassemia Non-carrier Bipolar Disorder Higher risk than average Blood Pressure (hypertension) Average risk Celiac Disease Higher risk than average Colorectal Cancer Average risk Cystic Fibrosis Non-carrier Heart Disease Average risk Lactose Intolerance Average risk Lung Cancer Lower risk than average Melanoma Average risk Obesity Average risk Resistance to HIV/AIDS Resistant to infection Schizophrenia Average risk Type 2 Diabetes Average risk Results from the 23andMe “Spit Kit” (Sample #2) Beta Thalassemia Non-carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Average risk Celiac Disease Average risk Colorectal Cancer Higher risk than average Cystic Fibrosis Carrier Heart Disease Average risk Lactose Intolerance Average risk Lung Cancer Average risk Melanoma Average risk Obesity Lower risk than average Resistance to HIV/AIDS Resistant to infection Schizophrenia Average risk Type 2 Diabetes Average risk

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Results from the 23andMe “Spit Kit” (Sample #3) Beta Thalassemia Non-carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Average risk Celiac Disease Average risk Colorectal Cancer Average risk Cystic Fibrosis Non-carrier Heart Disease Higher risk than average Lactose Intolerance Higher risk than average Lung Cancer Average risk Melanoma Lower risk than average Obesity Average risk Resistance to HIV/AIDS Resistant to infection Schizophrenia Average risk Type 2 Diabetes Average risk Results from the 23andMe “Spit Kit” (Sample #4) Beta Thalassemia Non-carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Higher risk than average Celiac Disease Average risk Colorectal Cancer Average risk Cystic Fibrosis Non–carrier Heart Disease Average risk Lactose Intolerance Average risk Lung Cancer Lower risk than average Melanoma Average risk Obesity Average risk Resistance to HIV/AIDS Resistant to infection Schizophrenia Average risk Type 2 Diabetes Higher risk than average

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Results from the 23andMe “Spit Kit” (Sample #5) Beta Thalassemia Carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Average risk Celiac Disease Higher risk than average Colorectal Cancer Average risk Cystic Fibrosis Non-carrier Heart Disease Average risk Lactose Intolerance Average risk Lung Cancer Average risk Melanoma Average risk Obesity Lower risk than average Resistance to HIV/AIDS Not resistant to infection Schizophrenia Average risk Type 2 Diabetes Average risk Results from the 23andMe “Spit Kit” (Sample #6) Beta Thalassemia Non-carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Average risk Celiac Disease Average risk Colorectal Cancer Average risk Cystic Fibrosis Carrier Heart Disease Average risk Lactose Intolerance Average risk Lung Cancer Higher risk than average Melanoma Lower risk than average Obesity Average risk Resistance to HIV/AIDS Not resistant to infection Schizophrenia Average risk Type 2 Diabetes Average risk

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Results from the 23andMe “Spit Kit” (Sample #7) Beta Thalassemia Non-carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Average risk Celiac Disease Average risk Colorectal Cancer Average risk Cystic Fibrosis Non-carrier Heart Disease Average risk Lactose Intolerance Higher risk than average Lung Cancer Lower risk than average Melanoma Average risk Obesity Higher risk than average Resistance to HIV/AIDS Not resistant to infection Schizophrenia Average risk Type 2 Diabetes Average risk Results from the 23andMe “Spit Kit” (Sample #8) Beta Thalassemia Non-carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Average risk Celiac Disease Average risk Colorectal Cancer Average risk Cystic Fibrosis Non-carrier Heart Disease Average risk Lactose Intolerance Average risk Lung Cancer Average risk Melanoma Average risk Obesity Lower risk than average Resistance to HIV/AIDS Not resistant to infection Schizophrenia Higher risk than average Type 2 Diabetes Higher risk than average

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Results from the 23andMe “Spit Kit” (Sample #9) Beta Thalassemia Non-carrier Bipolar Disorder Average risk Blood Pressure (hypertension) Average risk Celiac Disease Average risk Colorectal Cancer Average risk Cystic Fibrosis Non-carrier Heart Disease Average risk Lactose Intolerance Average risk Lung Cancer Lower risk than average Melanoma Higher risk than average Obesity Average risk Resistance to HIV/AIDS Not resistant to infection Schizophrenia Average risk Type 2 Diabetes Higher risk than average

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Appendix II Online sources for researching non-Mendelian diseases/traits http://health.nih.gov/ National Institutes of Health: the nation’s medical research agency. Browse general health topics alphabetically. http://www.cdc.gov/DiseasesConditions/ Centers for Disease Control and Prevention. Alphabetical, cross-referenced collection of information on diseases and conditions. www.geneticalliance.org Genetic Alliance: not-for-profit organization providing information to genetic consumers, researchers, and industry. Listings of genetic diseases as well as corresponding organizations. www.kumc.edu/gec/support/ University of Kansas Medical Center. Listing of rare and genetic conditions and information. http://www.mayoclinic.org/diseases-conditions Mayo Clinic. Consumer health site with symptom and treatment information on many common and rare diseases. www.medicinenet.com MedicineNet. Informational database of diseases, symptoms, procedures, and tests. http://www.webmd.com/ WebMD. Informational database of health information. http://blog.23andme.com/wp-content/uploads/2012/05/HeritabilityWithKids.jpg 23andMe. Heritability estimates of common diseases from 23andMe’s customer data.

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Appendix III Genetic Trait/Disease FAQ Sheet for Patients

Name of disease or trait: _________________________________________________

1) Are there any demographic risk factors (e.g., gender, ethnicity, age) associated with this disease/trait? 2) Are there any behavioral (e.g., smoking) or environmental (e.g., exposure to UV light) factors associated with this

disease/trait? 3) If yes, approximately how much does genetics contribute to this disease/trait (i.e., how heritable is the disease/

trait)? 4) Do most patients develop this disease/trait at a certain age? If yes, how old are they? 5) What are the most common symptoms or phenotypes associated with this disease/trait? How long do they last? 6) Are there preventive measures that people can take to avoid the onset of this disease/trait?

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R. Banks, C. Engelman, ASHG GENA 2008 Cohort

7) What behavioral or environmental modifications can patients make to control their symptoms? 8) Are there any treatments for this disease/trait? Is there a cure for this disease/trait? 9) What sources can patients turn to for more information?

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Appendix IV - 23andMe Sample Disease and Trait Reports

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Overview Community (92)

Celiac Disease: Preliminary Research

Celiac disease is an autoimmune disorder in which the body’s defenses treat wheat gluten as a pathogen, leading to an inflammatory response inthe small intestine. This response inhibits digestion and can lead to symptoms such as diarrhea, gas and fatigue. Celiac disease is estimated to occurin about 0.4% of people of European descent, although it is also considered under-diagnosed in the US. The disease has a substantial geneticcomponent, though exactly how much is unknown.

This is a "Preliminary Research" report, which means the associations presented below still need to be confirmed by the scientific community. Thereis also an "Established Research" report on Celiac Disease that covers well-established associations for this condition.

The following results are based on Preliminary Research for 1 reported marker.

Printable Version

Show results for all profilesCeliac disease

Citations

Cirillo G et al. (2007) . “Do MYO9B genetic variants predispose to coeliac disease? An association study in a cohort of South Italian children.” Dig Liver Dis 39(3):228-31.

Núñez C et al. (2006) . “No evidence of association of the MYO9B polymorphisms with celiac disease in the Spanish population.” Tissue Antigens 68(6):489-92.

Hunt KA et al. (2006) . “Lack of association of MYO9B genetic variants with coeliac disease in a British cohort.” Gut 55(7):969-72.

Monsuur AJ et al. (2005) . “Myosin IXB variant increases the risk of celiac disease and points toward a primary intestinal barrier defect.” Nat Genet 37(12):1341-4.

Journal Dig Liver Dis

Study Size

Replications None

Contrary Studies 3

Applicable Ethnicities European

Marker rs2305767

This study examined 463 individuals with celiac disease and 686healthy controls. The authors found that people with a C at both copiesof rs2305767 had 2.3 times lower odds for celiac disease than thosewith the TT genotype.

Who Genotype Genetic Result

Greg Mendel (Dad),Lilly Mendel (Mom) TT Slightly higher odds of celiac

disease.

CT Typical odds of celiac disease.

CC Moderately lower odds of celiacdisease.

The genotyping services of 23andMe are performed in LabCorp's CLIA-certified laboratory. The tests have not been cleared or approved by the FDA but have beenanalytically validated according to CLIA standards. The information on this page is intended for research and educational purposes only, and is not for diagnostic use.

HEALTH RESULTS

Health OverviewHealth RisksDrug ResponseInherited ConditionsTraitsHealth Tools

ANCESTRY RESULTS

Ancestry OverviewAncestry CompositionMaternal LinePaternal LineNeanderthal AncestryAncestry Tools

FAMILY & FRIENDS

Family TreeDNA RelativesFamily TraitsManage Sharing

RESEARCH & COMMUNITY

SurveysQuick QuestionsDiscoveriesInitiativesCommunity

GIFT A KIT

Buy additional kits orJoin our referralprogram

HEALTH RISKS CELIAC DISEASE: PRELIMINARY RESEARCH RATE

HOME MY RESULTS FAMILY & FRIENDS RESEARCH & COMMUNITY

Katherine Lontok

https://www.23andme.com/you/journal/legend2/ 1/1

Appendix V - 23andMe Marker Legend

Research Confidence

Established Research. At least two studies examined more than 750 people with the trait or conditionand/or the associations are widely accepted in the scientific community. The reports may cover rareconditions or include variants that do not greatly influence a person's absolute lifetime risk for acondition.

Preliminary Research. More than 750 people with the condition were studied, but the findings still needto be confirmed by the scientific community in an independent study of similar size.

Preliminary Research. Fewer than 750 people were studied. Multiple large studies are needed to confirmthese findings.

Preliminary Research. Fewer than 100 people were studied. Multiple large studies are needed to confirmthese findings.

R. Banks, C. Engelman, ASHG GENA 2008 Cohort

Appendix VI Name of disease or trait: _________________________________________________

Answer the following questions in complete thoughts. 1) For the disease/trait you are researching, how many total markers does 23andMe test for? How many are estab-

lished versus preliminary research reports? 2) What is the difference between an Established Research Report marker and a Preliminary Research Report mark-

er? Is the link to a disease/trait more valid for one versus the other? 3) Are there other known or unknown genetic factors that 23andMe does not test for that contribute to your overall

genetic risk for developing this disease/trait? Cite your source(s). 4) Given the ethnicity(ies) used to study the marker(s) linked to your disease/trait, how relevant is the report to you

specifically? Justify your answer. 5) Certain genotypes for each marker are associated with either increased or decreased genetic risk of developing

your disease/trait. What is “increased” or “decreased” risk relative to? 6) Will the risk assessment reported to you for this disease/trait influence your future behavior? If so, how?

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Appendix VII

Reading Guide for DNA: Promise and Peril For all the following questions, provide evidence from the reading, such as which paragraph, quotes, etc., where it is appropriate to do so. The reading guide is intended to help you to more carefully consider the content, intent, and rele-vance of the reading. 1) What is the main topic of this section? 2) What is/are the ethical, legal, or social component(s) of this issue? 3) Does anything from this chapter resonate with your own personal experience? 4) Briefly describe how your understanding of the topic changed as you read the chapter. 5) What thoughts or questions would you like to have shared or asked the authors that are relevant to the content of

the chapter?

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