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Original article| Volume 90, ISSUE 10, P1327-1337, October 01, 2015

Whole-Exome Sequencing of 10 Scientists: Evaluation of the Process and Outcomes

DOI:https://doi.org/10.1016/j.mayocp.2015.05.021
Whole-Exome Sequencing of 10 Scientists: Evaluation of the Process and Outcomes
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      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.

      Abbreviations and Acronyms:

      GATK (Genome Analysis Toolkit), HGMD (Human Mutation Database), IRB (institutional review board), VUS (variants of uncertain significance), WES (whole-exome sequencing)
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      Article Info

      Footnotes

      For editorial comment, see page 1311; for a related article, see page 1323

      Grant Support: This project was supported by the Mayo Clinic Center for Individualized Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Mayo Clinic Center for Individualized Medicine.

      Identification

      DOI: https://doi.org/10.1016/j.mayocp.2015.05.021

      Copyright

      © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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