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Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells

Author

Listed:
  • Brock A. Peters

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Bahram G. Kermani

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Andrew B. Sparks

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA
    Present addresses: Aria Diagnostics, 5945 Optical Court, San Jose, California 95138, USA (A.B.S.); Halo Genomics, Dag Hammarskjolds vag 54A, 751 83 Uppsala, Sweden (F.D.).)

  • Oleg Alferov

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Peter Hong

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Andrei Alexeev

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Yuan Jiang

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Fredrik Dahl

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA
    Present addresses: Aria Diagnostics, 5945 Optical Court, San Jose, California 95138, USA (A.B.S.); Halo Genomics, Dag Hammarskjolds vag 54A, 751 83 Uppsala, Sweden (F.D.).)

  • Y. Tom Tang

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Juergen Haas

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Kimberly Robasky

    (Harvard Medical School
    Program in Bioinformatics, Boston University)

  • Alexander Wait Zaranek

    (Harvard Medical School)

  • Je-Hyuk Lee

    (Harvard Medical School
    Wyss Institute for Biologically Inspired Engineering, Harvard Medical School)

  • Madeleine Price Ball

    (Harvard Medical School)

  • Joseph E. Peterson

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Helena Perazich

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • George Yeung

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Jia Liu

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Linsu Chen

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Michael I. Kennemer

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Kaliprasad Pothuraju

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Karel Konvicka

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Mike Tsoupko-Sitnikov

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Krishna P. Pant

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Jessica C. Ebert

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Geoffrey B. Nilsen

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Jonathan Baccash

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • Aaron L. Halpern

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

  • George M. Church

    (Harvard Medical School)

  • Radoje Drmanac

    (Complete Genomics, Inc., 2071 Stierlin Court, Mountain View, California 94043, USA)

Abstract

Recent advances in whole-genome sequencing have brought the vision of personal genomics and genomic medicine closer to reality. However, current methods lack clinical accuracy and the ability to describe the context (haplotypes) in which genome variants co-occur in a cost-effective manner. Here we describe a low-cost DNA sequencing and haplotyping process, long fragment read (LFR) technology, which is similar to sequencing long single DNA molecules without cloning or separation of metaphase chromosomes. In this study, ten LFR libraries were made using only ∼100 picograms of human DNA per sample. Up to 97% of the heterozygous single nucleotide variants were assembled into long haplotype contigs. Removal of false positive single nucleotide variants not phased by multiple LFR haplotypes resulted in a final genome error rate of 1 in 10 megabases. Cost-effective and accurate genome sequencing and haplotyping from 10–20 human cells, as demonstrated here, will enable comprehensive genetic studies and diverse clinical applications.

Suggested Citation

  • Brock A. Peters & Bahram G. Kermani & Andrew B. Sparks & Oleg Alferov & Peter Hong & Andrei Alexeev & Yuan Jiang & Fredrik Dahl & Y. Tom Tang & Juergen Haas & Kimberly Robasky & Alexander Wait Zaranek, 2012. "Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells," Nature, Nature, vol. 487(7406), pages 190-195, July.
    • Handle: RePEc:nat:nature:v:487:y:2012:i:7406:d:10.1038_nature11236
    DOI: 10.1038/nature11236
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