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Whole genome–amplified DNA: insights and imputation

Nature Methods volume 5, pages 279–280 (2008)Cite this article

To the editor:

Genome-wide association studies (GWAS) have enabled a considerable portion of the human genome to be scanned for genetic variants associated with disease etiology. Such large-scale investigations depend on DNA samples of high biological integrity and quality. As clinical DNA is often available in limited quantities, in vitro reproduction of quality template DNA using whole-genome amplification is necessary. The most widely used technique is multiple displacement amplification with φ29 polymerase1 (φ29MDA). Earlier studies do not offer a detailed map of how robust genome-wide panels of 300,000 to 1 million single-nucleotide polymorphisms (SNPs) will perform with φ29MDA2,3. We performed a meta-analysis of 6,541 DNA samples to assess the extent of information lost (Supplementary Table 1 online), and investigated genotype imputation for recovering the statistical power and genomic coverage of GWAS (Supplementary Methods online).

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Figure 1: Missingness and imputation of amplified DNA on chromosome 16.

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Author notes

  1. Yik Y Teo and Michael Inouye: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Yik Y Teo, Kerrin S Small, Andrew E Fry, Kirk A Rockett & Dominic P Kwiatkowski

  2. Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, Cambridge, UK

    Yik Y Teo, Michael Inouye, Kerrin S Small, Simon C Potter, Dominic P Kwiatkowski & Panos Deloukas

  3. Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

    Sarah J Dunstan

  4. Genome Institute of Singapore, Agency for Science, Technology and Research, 60 Biopolis Street, 138672, Singapore

    Mark Seielstad

  5. MRC Epidemiology Unit, Strangeways Research Laboratories, Worts Causeway, CB1 8RN, Cambridge, UK

    Inês Barroso

  6. Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, Cambridge, UK

    Nicholas J Wareham

Authors
  1. Yik Y Teo
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  2. Michael Inouye
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  3. Kerrin S Small
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  4. Andrew E Fry
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  5. Simon C Potter
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  6. Sarah J Dunstan
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  7. Mark Seielstad
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  8. Inês Barroso
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  9. Nicholas J Wareham
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  10. Kirk A Rockett
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  11. Dominic P Kwiatkowski
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  12. Panos Deloukas
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Corresponding author

Correspondence to Panos Deloukas.

Supplementary information

Supplementary Text and Figures

Supplementary Tables 1–3, Supplementary Figures 1–5, Supplementary Methods (PDF 894 kb)

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Teo, Y., Inouye, M., Small, K. et al. Whole genome–amplified DNA: insights and imputation. Nat Methods 5, 279–280 (2008). https://doi.org/10.1038/nmeth0408-279

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