Noralane M Lindor1, Kimberly A Schahl2, Kiley J Johnson2, Katherine S Hunt3, Kara A Mensink4, Eric D Wieben5, Eric Klee6, John L Black7, W Edward Highsmith7, Stephen N Thibodeau7, Matthew J Ferber7, Umut Aypar7, Yuan Ji7, Rondell P Graham7, Alexander S Fiksdal8, Vivek Sarangi6, Kelly E Ormond9, Douglas L Riegert-Johnson10, Tammy M McAllister4, Gianrico Farrugia11, Jennifer B McCormick12. 1. Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ; Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ. Electronic address: nlindor@mayo.edu. 2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; Center for Individualized Medicine, Mayo Clinic, Rochester, MN. 3. Center for Individualized Medicine, Mayo Clinic, Scottsdale, AZ; Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ. 4. Center for Individualized Medicine, Mayo Clinic, Rochester, MN. 5. Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN. 6. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN. 7. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. 8. Department of Psychology, Brandeis University, Waltham, MA. 9. Department of Genetics and Stanford Center for Biomedical Ethics, Stanford School of Medicine, Stanford, CA. 10. Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL. 11. Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. 12. Biomedical Ethics Program, Mayo Clinic, Rochester, MN; Division of General Internal Medicine, Mayo Clinic, Rochester, MN.
Abstract
OBJECTIVE: To understand motivations, educational needs, and concerns of individuals contemplating whole-exome sequencing (WES) and determine what amount of genetic information might be obtained by sequencing a generally healthy cohort so as to more effectively counsel future patients. PATIENTS AND METHODS: From 2012 to 2014, 40 medically educated, generally healthy scientists at Mayo Clinic were invited to have WES conducted on a research basis; 26 agreed to be in a drawing from which 10 participants were selected. The study involved pre- and posttest genetic counseling and completion of 4 surveys related to the experience and outcomes. Whole-exome sequencing was conducted on DNA from blood from each person. RESULTS: Most variants (76,305 per person; range, 74,505-77,387) were known benign allelic variants, variants in genes of unknown function, or variants of uncertain significance in genes of known function. The results of suspected pathogenic/pathogenic variants in Mendelian disorders and pharmacogenomic variants were disclosed. The mean number of suspected pathogenic/pathogenic variants was 2.2 per person (range, 1-4). Four pharmacogenomic genes were included for reporting; variants were found in 9 of 10 participants. CONCLUSION: This study provides data that may be useful in establishing reality-based patient expectations, outlines specific points to cover during counseling, and increases confidence in the feasibility of providing adequate preparation and counseling for WES in generally healthy individuals.
OBJECTIVE: To understand motivations, educational needs, and concerns of individuals contemplating whole-exome sequencing (WES) and determine what amount of genetic information might be obtained by sequencing a generally healthy cohort so as to more effectively counsel future patients. PATIENTS AND METHODS: From 2012 to 2014, 40 medically educated, generally healthy scientists at Mayo Clinic were invited to have WES conducted on a research basis; 26 agreed to be in a drawing from which 10 participants were selected. The study involved pre- and posttest genetic counseling and completion of 4 surveys related to the experience and outcomes. Whole-exome sequencing was conducted on DNA from blood from each person. RESULTS: Most variants (76,305 per person; range, 74,505-77,387) were known benign allelic variants, variants in genes of unknown function, or variants of uncertain significance in genes of known function. The results of suspected pathogenic/pathogenic variants in Mendelian disorders and pharmacogenomic variants were disclosed. The mean number of suspected pathogenic/pathogenic variants was 2.2 per person (range, 1-4). Four pharmacogenomic genes were included for reporting; variants were found in 9 of 10 participants. CONCLUSION: This study provides data that may be useful in establishing reality-based patient expectations, outlines specific points to cover during counseling, and increases confidence in the feasibility of providing adequate preparation and counseling for WES in generally healthy individuals.
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