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Assessing the utility of whole genome amplified DNA as a template for DMET Plus array

  • Yi Jing He , Anne D. Misher , William Irvin , Alison Motsinger-Reif , Howard L. McLeod and Janelle M. Hoskins EMAIL logo
Published/Copyright: February 14, 2012
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Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 50 Issue 8

Abstract

Background: Large amounts of high quality DNA are typically required for high-throughput genotyping arrays but sometimes study participant DNA is in limited supply. Multiple displacement amplification (MDA)-based whole genome amplification is an in vitro technique that permits the genetic analysis of limited amounts of high molecular weight genomic DNA (gDNA).

Methods: The performance of MDA-whole genome amplified DNA (wgaDNA) as a template for DMET Plus (Affymetrix) was assessed. wgaDNA was generated from gDNA from three HapMap CEU cell lines and 11 breast cancer patients. One HapMap sample and three patient samples were randomly selected for replication to assess reproducibility. Accuracy was assessed by comparing the wgaDNA genotypes with gDNA genotypes. The kappa (κ) statistic was used to measure genotype concordance between paired gDNA-wgaDNA and wgaDNA-wgaDNA samples. Copy number variants (CNV) were not included in concordance analysis in this study.

Results: A good genotype call rate of 98.8%±1.06% (mean±standard deviation, 1931 markers) was observed for all 18 wgaDNA samples with three samples having call rates lower than 98%. High genotype concordance rates were observed between four HapMap wgaDNA-gDNA pairs (98.5%, κ=0.9817, p<0.0001, 1931 markers) and 14 patient wgaDNA-gDNA pairs (100%, κ=1.00, p<0.0001, 19 markers among CYP2D6 and CYP2C19). Excellent genotype concordance was also observed between four independently amplified duplicate samples (98.0%, κ=0.9745; p<0.0001, 1931 markers).

Conclusions: MDA-produced wgaDNA provides accurate and reproducible genotypes with the DMET Plus array and is therefore a suitable template for this targeted pharmacogenetic genotyping array.

Keywords: ADME; array; CYP2D6; DMET Plus; pharmacogenetics; pharmacogenomics; whole genome amplification
Corresponding author: Janelle M. Hoskins, Gentris Corporation, 133 Southcenter Court, Morrisville, NC 27560, USA Phone: +1 919 6787023, Fax: +1 919 4650554
Received: 2011-10-13
Accepted: 2012-1-17
Published Online: 2012-02-14
Published in Print: 2012-08-01

©2012 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2011-0747
Keywords for this article
ADME; array; CYP2D6; DMET Plus; pharmacogenetics; pharmacogenomics; whole genome amplification

Articles in the same Issue

  1. Masthead
  2. Masthead
  3. Editorial
  4. EDTA-dependent pseudothrombocytopenia: further insights and recommendations for prevention of a clinically threatening artifact
  5. Reviews
  6. Mitochondria as sources and targets of damage in cellular aging
  7. Application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in Alzheimer’s disease
  8. Opinion Papers
  9. The intellectual contribution of laboratory medicine professionals to research papers on laboratory medicine topics published in high-impact general medicine journals
  10. Laboratory medicine and sports: between Scylla and Charybdis
  11. Guidelines and Recommendations
  12. The EC4 European Syllabus for Post-Graduate Training in Clinical Chemistry and Laboratory Medicine: version 4 – 2012
  13. Genetics And Molecular Diagnostics
  14. Assessing the utility of whole genome amplified DNA as a template for DMET Plus array
  15. General Clinical Chemistry And Laboratory Medicine
  16. Effect of acceleration forces during transport through a pneumatic tube system on ROTEM® analysis
  17. The transferrin/log(ferritin) ratio: a new tool for the diagnosis of iron deficiency anemia
  18. Instructions on laboratory monitoring in 200 drug labels
  19. Lipid peroxidation markers in Crohn’s disease: the associations and diagnostic value
  20. Impact of asthmatic control status on serum cystatin C concentrations
  21. Elevated levels of Nɛ-homocysteinyl-lysine isopeptide in patients on long-term hemodialysis
  22. Interleukin-1α gene variants influence bone mineral density and the risk of osteoporotic hip fractures in elderly Slovenian people
  23. Novel method to dissociate platelet clumps in EDTA-dependent pseudothrombocytopenia based on the pathophysiological mechanism
  24. Proficiency testing/external quality assurance for the PFA-100®
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  26. Infectious Diseases
  27. Monocyte chemoattractant protein-1 and paraoxonase-1 and 3 levels in patients with sepsis treated in an intensive care unit: a preliminary report
  28. Association between ischemia-modified albumin, homocysteine, vitamin B12 and folic acid in patients with severe sepsis
  29. Evidence for serum miR-15a and miR-16 levels as biomarkers that distinguish sepsis from systemic inflammatory response syndrome in human subjects
  30. The predictive value of immature granulocyte count and immature myeloid information in the diagnosis of neonatal sepsis
  31. Hypophosphatemia, fever and prolonged length of hospital stay in seronegative PCR positive patients as compared to seropositive patients with early acute Q fever pneumonia
  32. Cancer Diagnostics
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