Evidence That Personal Genome Testing Enhances Student Learning in a Course on Genomics and Personalized Medicine

An emerging debate in academic medical centers is not about the need for providing trainees with fundamental education on genomics, but rather the most effective educational models that should be deployed. At Stanford School of Medicine, a novel hands-on genomics course was developed in 2010 that provided students the option to undergo personal genome testing as part of the course curriculum. We hypothesized that use of personal genome testing in the classroom would enhance the learning experience of students. No data currently exist on how such methods impact student learning; thus, we surveyed students before and after the course to determine its impact. We analyzed responses using paired statistics from the 31 medical and graduate students who completed both pre-course and post-course surveys. Participants were stratified by those who did (N = 23) or did not (N = 8) undergo personal genome testing. In reflecting on the experience, 83% of students who underwent testing stated that they were pleased with their decision compared to 12.5% of students who decided against testing (P = 0.00058). Seventy percent of those who underwent personal genome testing self-reported a better understanding of human genetics on the basis of having undergone testing. Further, students who underwent personal genome testing demonstrated an average 31% increase in pre- to post-course scores on knowledge questions (P = 3.5×10−6); this was significantly higher (P = 0.003) than students who did not undergo testing, who showed a non-significant improvement. Undergoing personal genome testing and using personal genotype data in the classroom enhanced students' self-reported and assessed knowledge of genomics, and did not appear to cause significant anxiety. At least for self-selected students, the incorporation of personal genome testing can be an effective educational tool to teach important concepts of clinical genomic testing.

1. In an article published this year in the New England Journal of Medicine, whole-genome sequencing was performed on an individual with autosomal recessive Charcot-Marie-Tooth (CMT) disease. Mutations in the SH3TC2 gene were identified as the causal mutations. The genotype of the proband was R954X/Y169H. The genetic basis of CMT discovered in this family is an example of: (a) variable expressivity (b) incomplete penetrance (c) genetic mosaicism (d) compound heterozygosity (e) I do not know the answer to this question 2. A 34-year-old female of Northern European ancestry presents in your clinic with a strong family history of breast and ovarian cancer on both sides of the family. She brings along the results of her personal genomics testing by a direct-to-consumer (DTC) genetics company. Your patient's DTC genetics profile indicates she does not carry any of the 3 BRCA1 or BRCA2 mutations tested. Additionally, based on 3 other tested SNPs found to be associated with breast cancer in recent genome-wide association studies, her report reveals a risk of 9.1% compared to the average of 12.5%. What is the appropriate conclusion?
(a) The patient has below-average risk but should continue regular screening measures (b) The patient has the same risk of breast cancer as the average woman of her ethnicity and should continue regular screening measures (c) The patient has above-average risk and should consider getting her BRCA1 gene sequenced (d) The patient has above-average risk and should consider getting her BRCA1 and BRCA2 genes sequenced (e) I do not know the answer to this question 3. The patient in question 3 is diagnosed with invasive breast cancer at age 38. Her cancer is most likely due to: (a) an inherited founder mutation in BRCA1 (b) an inherited founder mutation in BRCA2 (c) an inherited non-founder mutation in BRCA1 (d) non-hereditary factors (e) I do not know the answer to this question Patient A is a 45-year-old white male who presents to your clinic with an unremarkable medical history. He has recently undergone personal genotyping by a DTC genetics company and comes to your office concerned about his risk of getting a heart attack.
According to the company, "numerous SNPs associated with one's chances of a heart attack have been found in the chromosomal region 9p21. [We] report your results for a SNP that is linked to the most strongly associated SNP in this region." Your patient's genotype for this SNP (rs2383207) is G/G and the DTC genetics company calculates his risk of a heart attack to be elevated at 24.8%, compared to the average risk of 21.2% for men of European descent in the United States.
Based on individuals of European descent genotyped as part of the International HapMap project, the following table shows the genotype frequencies for rs2383207 in the population.

A/A A/G G/G
Section II: Attitudes about personal genotyping 1. If you were to ever undergo personal genotyping in the future, would you ask a health care provider for help in interpreting the results?

Genetics 210 Post-Course Survey (Not Genotyped) Section III: Knowledge of personal genomic testing
Please select the most appropriate answer choice.
1. In an article published this year in the New England Journal of Medicine, whole-genome sequencing was performed on an individual with autosomal recessive Charcot-Marie-Tooth (CMT) disease. Mutations in the SH3TC2 gene were identified as the causal mutations. The genotype of the proband was R954X/Y169H. The genetic basis of CMT discovered in this family is an example of: (a) variable expressivity (b) incomplete penetrance (c) genetic mosaicism (d) compound heterozygosity (e) I do not know the answer to this question 2. A 34-year-old female of Northern European ancestry presents in your clinic with a strong family history of breast and ovarian cancer on both sides of the family. She brings along the results of her personal genomics testing by a direct-to-consumer (DTC) genetics company. Your patient's DTC genetics profile indicates she does not carry any of the 3 BRCA1 or BRCA2 mutations tested. Additionally, based on 3 other tested SNPs found to be associated with breast cancer in recent genome-wide association studies, her report reveals a risk of 9.1% compared to the average of 12.5%. What is the appropriate conclusion?
(a) The patient has below-average risk but should continue regular screening measures (b) The patient has the same risk of breast cancer as the average woman of her ethnicity and should continue regular screening measures (c) The patient has above-average risk and should consider getting her BRCA1 gene sequenced (d) The patient has above-average risk and should consider getting her BRCA1 and BRCA2 genes sequenced (e) I do not know the answer to this question 3. The patient in question 3 is diagnosed with invasive breast cancer at age 38. Her cancer is most likely due to: (a) an inherited founder mutation in BRCA1 (b) an inherited founder mutation in BRCA2 (c) an inherited non-founder mutation in BRCA1 (d) non-hereditary factors (e) I do not know the answer to this question Patient A is a 45-year-old white male who presents to your clinic with an unremarkable medical history. He has recently undergone personal genotyping by a DTC genetics company and comes to your office concerned about his risk of getting a heart attack.
According to the company, "numerous SNPs associated with one's chances of a heart attack have been found in the chromosomal region 9p21.
[We] report your results for a SNP that is linked to the most strongly associated SNP in this region." Your patient's genotype for this SNP (rs2383207)   Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 11. I felt that I was at a disadvantage in the class because the professors knew whether I had undergone personal genotyping.
 Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 12. With regards to the offer of personal genotyping as part of a curriculum, which of the following best reflects your beliefs:  Personal genotyping should be required for all medical students and graduate students in the core curriculum (GENE 202/203)  Personal genotyping should be made available on an optional basis for all medical students and graduate students in the core curriculum (GENE 202/203)  Personal genotyping should be made available on an optional basis for medical students and graduate students in elective classes such as GENE 210  Personal genotyping should not be made available as part of a course, but could be offered to students in an optional manner through other venues  Personal genotyping should not be made available to students in any formal manner.

Section I: Basic information
1. How many class meetings of Genetics 210 did you attend?

Section III: Knowledge of personal genomic testing
Please select the most appropriate answer choice.
1. In an article published this year in the New England Journal of Medicine, whole-genome sequencing was performed on an individual with autosomal recessive Charcot-Marie-Tooth (CMT) disease. Mutations in the SH3TC2 gene were identified as the causal mutations. The genotype of the proband was R954X/Y169H. The genetic basis of CMT discovered in this family is an example of: (a) variable expressivity (b) incomplete penetrance (c) genetic mosaicism (d) compound heterozygosity (e) I do not know the answer to this question 2. A 34-year-old female of Northern European ancestry presents in your clinic with a strong family history of breast and ovarian cancer on both sides of the family. She brings along the results of her personal genomics testing by a direct-to-consumer (DTC) genetics company. Your patient's DTC genetics profile indicates she does not carry any of the 3 BRCA1 or BRCA2 mutations tested. Additionally, based on 3 other tested SNPs found to be associated with breast cancer in recent genome-wide association studies, her report reveals a risk of 9.1% compared to the average of 12.5%. What is the appropriate conclusion?
(a) The patient has below-average risk but should continue regular screening measures (b) The patient has the same risk of breast cancer as the average woman of her ethnicity and should continue regular screening measures (c) The patient has above-average risk and should consider getting her BRCA1 gene sequenced (d) The patient has above-average risk and should consider getting her BRCA1 and BRCA2 genes sequenced (e) I do not know the answer to this question  Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 18. I was able to easily go back and forth between my personal genotype dataset and the provided publicly available dataset as I worked on data analysis exercises.
 Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 19. I felt that the professors knew whether I had undergone personal genotyping.
 Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 20. I felt that I was at a disadvantage in the class because the professors knew whether I had undergone personal genotyping.
 Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 21. I felt required to divulge my genotype information in order to ask questions of the professors in Genetics 210.
 Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 22. I felt comfortable divulging my genotype information in order to ask questions of the professors in Genetics 210.
 Strongly disagree  Disagree  Neither agree nor disagree  Agree  Strongly agree 23. With regards to the offer of personal genotyping as part of a curriculum, which of the following best reflects your beliefs:  Personal genotyping should be required for all medical students and graduate students in the core curriculum (GENE 202/203)  Personal genotyping should be made available on an optional basis for all medical students and graduate students in the core curriculum (GENE 202/203)  Personal genotyping should be made available on an optional basis for medical students and graduate students in elective classes such as GENE 210  Personal genotyping should not be made available as part of a course, but could be offered to students in an optional manner through other venues  Personal genotyping should not be made available to students in any formal manner.