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Single Nucleotide Polymorphisms and Next Generation Sequencing

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Human Gametes and Preimplantation Embryos

Abstract

Single cell analysis for preimplantation genetic diagnosis (PGD) of single gene defects was first used to identify the sex of embryos in a series of couples at risk of various X-linked conditions, which typically only affect males. The use of PCR at the single cell level was still in its infancy and even doubling the typical number of amplification cycles failed to amplify unique target sequences reliably. For this reason, PCR amplification of a Y-linked repeat sequence, present in thousands of copies per cell, was used for identification of male embryos. However, the extreme sensitivity of this protocol and the rapid build-up of amplified DNA products in the laboratory environment, soon led to the appearance of contamination and false positive results in blank (negative) controls. Furthermore, in a minority of single male cells amplification still failed, resulting in a male embryo being identified as female, which lead to the first clinical misdiagnosis following PGD.

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Author information

Authors and Affiliations

  1. The Bridge Centre, London Bridge, London, UK

    Alan H. Handyside

  2. Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK

    Dagan Wells

  3. Institute of Reproductive Sciences, Oxford, UK

    Dagan Wells

Authors
  1. Alan H. Handyside
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  2. Dagan Wells
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Corresponding author

Correspondence to Dagan Wells .

Editor information

Editors and Affiliations

  1. University of Melbourne, Department of Zoology, Royal Parade, Melbourne, 3010, Victoria, Australia

    David K. Gardner

  2. Boston IVF, Second Ave. 130, Waltham, 02451, Massachusetts, USA

    Denny Sakkas

  3. Yale School of Medicine, Dept. of Ob/Gyn & Reproductive Sciences, Cedar St. 333, New Haven, 06510, Connecticut, USA

    Emre Seli

  4. Obstetrics & Gynaecology, University of Oxford, Nuffield Department of, Garsington Road, Oxford, OX4 2HW, Oxfordshire, United Kingdom

    Dagan Wells

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Handyside, A.H., Wells, D. (2013). Single Nucleotide Polymorphisms and Next Generation Sequencing. In: Gardner, D., Sakkas, D., Seli, E., Wells, D. (eds) Human Gametes and Preimplantation Embryos. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6651-2_12

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  • DOI: https://doi.org/10.1007/978-1-4614-6651-2_12

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6650-5

  • Online ISBN: 978-1-4614-6651-2

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