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

      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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      References

        • Plon S.E.
        • Eccles D.M.
        • Easton D.
        • et al.
        IARC Unclassified Genetic Variants Working Group. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results.
        Hum Mutat. 2008; 29: 1282-1291
      1. Ormond KE, Hudgins L, Caleshu C, Greely H, Lee SJ, Cho MK. Personal genotyping in genetics faculty members considering personal whole genome sequencing. Poster presented at: 12th International Congress of Human Genetics/61st Annual Meeting of the American Society of Human Genetics; October 5-11, 2011; Montreal, Quebec, Canada. Poster #1062.

      2. Ormond KE, Caleshu C, Hudgins L, Greely H, Lee SJ, Cho MK. Characteristics of healthy participants in a whole genome sequencing study. Poster presented at: 12th International Congress of Human Genetics/61st Annual Meeting of The American Society of Human Genetics; October 5-11, 2011; Montreal, Quebec, Canada. Poster #1056.

      3. Trzupek K, Trivedi A, Ormond KE, Sutphen R. Pre-test genetic counseling for whole genome sequencing: development of a protocol and evaluation of participant experience. Poster presented at: 12th International Congress of Human Genetics/61st Annual Meeting of The American Society of Human Genetics; October 11-15, 2011; Montreal, Quebec, Canada. Poster #1040.

        • Dewey F.E.
        • Grove M.E.
        • Pan C.
        • et al.
        Clinical interpretation and implications of whole-genome sequencing.
        JAMA. 2014; 311: 1035-1045
        • Green R.C.
        • Berg J.S.
        • Grody W.W.
        • et al.
        American College of Medical Genetics and Genomics. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.
        Genet Med. 2013; 15: 565-574
        • Gochee P.A.
        • Powell L.W.
        • Cullen D.J.
        • Du Sart D.
        • Rossi E.
        • Olynyk J.K.
        A population-based study of the biochemical and clinical expression of the H63D hemochromatosis mutation (published correction appears in Gastroenterology. 2002;122(4):1191).
        Gastroenterology. 2002; 122: 646-651
        • Dorschner M.O.
        • Amendola L.M.
        • Turner E.H.
        • et al.
        Actionable, pathogenic incidental findings in 1,000 participants' exomes.
        Am J Hum Genet. 2013; 93: 631-640