Two Methods of Whole-Genome Amplification Enable Accurate Genotyping Across a 2320-SNP Linkage Panel

  1. David L. Barker2,
  2. Mark S.T. Hansen2,
  3. A. Fawad Faruqi3,5,
  4. Diane Giannola4,
  5. Orlando R. Irsula1,
  6. Roger S. Lasken3,
  7. Martin Latterich2,6,
  8. Vladimir Makarov4,
  9. Arnold Oliphant2,
  10. Jonathon H. Pinter4,
  11. Richard Shen2,
  12. Irina Sleptsova4,
  13. William Ziehler4, and
  14. Eric Lai1,7
  1. 1 Genetics Research, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA
  2. 2 Illumina, Inc., San Diego, California 92121, USA
  3. 3 Molecular Staging, Inc., New Haven, Connecticut 06511, USA
  4. 4 Rubicon Genomics, Ann Arbor, Michigan 48108, USA

Abstract

Comprehensive genome scans involving many thousands of SNP assays will require significant amounts of genomic DNA from each sample. We report two successful methods for amplifying whole-genomic DNA prior to SNP analysis, multiple displacement amplification, and OmniPlex technology. We determined the coverage of amplification by analyzing a SNP linkage marker set that contained 2320 SNP markers spread across the genome at an average distance of 2.5 cM. We observed a concordance of >99.8% in genotyping results from genomic DNA and amplified DNA, strongly indicating the ability of both methods used to amplify genomic DNA in a highly representative manner. Furthermore, we were able to achieve a SNP call rate of >98% in both genomic and amplified DNA. The combination of whole-genome amplification and comprehensive SNP linkage analysis offers new opportunities for genetic analysis in clinical trials, disease association studies, and archiving of DNA samples.

Footnotes

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1949704.

  • 5 Present address: Trimgen Corporation, Sparks, Maryland 21152, USA

  • 6 Present address: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A 2B2, Canada.

  • 7 Corresponding author. E-MAIL eric.h.lai{at}gsk.com; FAX (919) 315-4174.

    • Accepted February 10, 2004.
    • Received September 8, 2003.
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