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Whole Genome Sequencing in the Clinical Laboratory

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Modern Clinical Molecular Techniques

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Abstract

With the advent of massively parallel sequencing (MPS) technologies, it is now possible to sequence an entire human genome for about the price it would cost to sequence four or five genes at comparable accuracy using Sanger sequencing methods. In this chapter, we discuss the opportunities and challenges of developing a MPS protocol for whole genome sequencing within a clinical laboratory as well as its potential applications for clinical use.

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References

  1. Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci USA. 1977;74:560–4.

    Article  PubMed  CAS  Google Scholar 

  2. Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975;94:441–8.

    Article  PubMed  CAS  Google Scholar 

  3. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA. 1977;74:5463–7.

    Article  PubMed  CAS  Google Scholar 

  4. Smith LM, Sanders JZ, Kaiser RJ, et al. Fluorescence detection in automated DNA sequence analysis. Nature. 1986;321:674–9.

    Article  PubMed  CAS  Google Scholar 

  5. Smith LM, Fung S, Hunkapiller MW, Hunkapiller TJ, Hood LE. The synthesis of oligonucleotides containing an aliphatic amino group at the 5′ terminus: synthesis of fluorescent DNA primers for use in DNA sequence analysis. Nucleic Acids Res. 1985;13:2399–412.

    Article  PubMed  CAS  Google Scholar 

  6. GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. http://www.genetests.org (1993–2011).

  7. Brenner S, et al. Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arrays. Nat Biotechnol. 2000;18:630–4.

    Article  PubMed  CAS  Google Scholar 

  8. Mardis ER. Next-generation DNA sequencing methods sequencing methods. Annu Rev Genomics Hum Genet. 2008;9:387–402.

    Article  PubMed  CAS  Google Scholar 

  9. Schuster SC. Next-generation sequencing transforms today’s biology. Nat Methods. 2008;5:16–8.

    Article  PubMed  CAS  Google Scholar 

  10. Ewing B, Green P. Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res. 1998;8:186–94.

    PubMed  CAS  Google Scholar 

  11. Ewing B, Hillier L, Wendl MC, Green P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res. 1998;8:175–85.

    PubMed  CAS  Google Scholar 

  12. Metzker M. Sequencing technologies—the next generation. Nat Rev Genet. 2010;11:31–46.

    Article  PubMed  CAS  Google Scholar 

  13. Shendure J, Ji H. Next-generation DNA sequencing. Nat Biotechnol. 2008;26:1135–45.

    Article  PubMed  CAS  Google Scholar 

  14. Department of Health and Human Services, Centers for Medicare & Medicaid Services. Clinical laboratory improvement amendments of 1988; final rule. Fed Register (1992), [42CFR493].

    Google Scholar 

  15. Laboratory General Checklist. College of American Pathologists, Northfield (2010).

    Google Scholar 

  16. Molecular Pathology Checklist. College of American Pathologists, Northfield (2010).

    Google Scholar 

  17. Centers for Disease Control and Prevention. Good laboratory practices for molecular genetic testing for heritable diseases and conditions. MMWR. 2009;58(No. RR-6):1–37.

    Google Scholar 

  18. Clinical and Laboratory Standards Institute. Nucleic acid sequencing methods in diagnostic laboratory medicine; Approved guideline. 2004; 24(40):MM9-A.

    Google Scholar 

  19. Maddalena A, Bale S, Das S, et al. Technical standards and guidelines: molecular genetic testing for ultra-rare disorders. Genet Med. 2005;7:571–83.

    Article  PubMed  Google Scholar 

  20. Das S, Bale S, Ledbetter D. Molecular genetic testing for ultra rare diseases: models for translation from the research laborabory to the CLIA-certified diagnostic laboratory. Genet Med. 2008;10:332–6.

    Article  PubMed  CAS  Google Scholar 

  21. Huntington’s Disease Society of America, Inc. Guidelines for genetic testing for Huntington’s disease. Copyright 2008 by Hereditary Disease Foundation. http://www.hdfoundation.org/html/hdsatest.php.

  22. Nowrousian M, Stajich JE, Chu M, et al. De Novo assembly of a 40 Mb Eukaryotic genome from short sequence reads: Sordaria macrospora, a model organism for fungal morphogenesis. PLoS Genet. 2010;6(4):e1000891, 1–22.

    Article  PubMed  Google Scholar 

  23. Martinez DA, Nelson MA. The next generation becomes the now generation. PLoS Genet. 2010;6:e1000906, 1–3.

    Article  PubMed  Google Scholar 

  24. Jones SJM, Laskin J, Li YY, et al. Evolution of an adenocarcinoma in response to selection by targeted kinase inhibitors. Genome Biol. 2010;11(R82):1–12.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Illumina Clinical Services Laboratory, Illumina, Inc., 9885 Towne Centre Dr., San Diego, CA, 92122, USA

    Tina Hambuch Ph.D., Brad Sickler M.S., Arnold Liao M.P.H., Suneer Jain MS, MB(ASCP)CM, CGMBS & Philip D. Cotter Ph.D., FACMG, FFSc(RCPA)

Authors
  1. Tina Hambuch Ph.D.
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  2. Brad Sickler M.S.
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  3. Arnold Liao M.P.H.
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  4. Suneer Jain MS, MB(ASCP)CM, CGMBS
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  5. Philip D. Cotter Ph.D., FACMG, FFSc(RCPA)
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Corresponding author

Correspondence to Tina Hambuch Ph.D. .

Editor information

Editors and Affiliations

  1. , Molecular Genetic Technology Program, M.D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 2, Houston, 77030, Texas, USA

    Peter Hu

  2. , Department of Human Genetics, Emory University School of Medicine, 615 Michael St. NE, Suite 315, Atlanta, 30322, Georgia, USA

    Madhuri Hegde

  3. , Molecular Genetic Technology Program, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 2, Houston, 77030, Texas, USA

    Patrick Alan Lennon

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Hambuch, T., Sickler, B., Liao, A., Jain, S., Cotter, P.D. (2012). Whole Genome Sequencing in the Clinical Laboratory. In: Hu, P., Hegde, M., Lennon, P. (eds) Modern Clinical Molecular Techniques. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-2170-2_5

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  • DOI: https://doi.org/10.1007/978-1-4614-2170-2_5

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-2169-6

  • Online ISBN: 978-1-4614-2170-2

  • eBook Packages: MedicineMedicine (R0)

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