Differences in AMY1 Gene Copy Numbers Derived from Blood, Buccal Cells and Saliva Using Quantitative and Droplet Digital PCR Methods: Flagging the Pitfall

PLoS One. 2017 Jan 26;12(1):e0170767. doi: 10.1371/journal.pone.0170767. eCollection 2017.

Abstract

Introduction: The human salivary (AMY1) gene, encoding salivary α-amylase, has variable copy number variants (CNVs) in the human genome. We aimed to determine if real-time quantitative polymerase chain reaction (qPCR) and the more recently available Droplet Digital PCR (ddPCR) can provide a precise quantification of the AMY1 gene copy number in blood, buccal cells and saliva samples derived from the same individual.

Methods: Seven participants were recruited and DNA was extracted from the blood, buccal cells and saliva samples provided by each participant. Taqman assay real-time qPCR and ddPCR were conducted to quantify AMY1 gene copy numbers. Statistical analysis was carried out to determine the difference in AMY1 gene copy number between the different biological specimens and different assay methods.

Results: We found significant within-individual difference (p<0.01) in AMY1 gene copy number between different biological samples as determined by qPCR. However, there was no significant within-individual difference in AMY1 gene copy number between different biological samples as determined by ddPCR. We also found that AMY1 gene copy number of blood samples were comparable between qPCR and ddPCR, while there is a significant difference (p<0.01) between AMY1 gene copy numbers measured by qPCR and ddPCR for both buccal swab and saliva samples.

Conclusions: Despite buccal cells and saliva samples being possible sources of DNA, it is pertinent that ddPCR or a single biological sample, preferably blood sample, be used for determining highly polymorphic gene copy numbers like AMY1, due to the large within-individual variability between different biological samples if real time qPCR is employed.

MeSH terms

  • Adolescent
  • Adult
  • DNA / genetics*
  • DNA / isolation & purification
  • DNA Copy Number Variations
  • Gene Dosage*
  • Gene Expression
  • Humans
  • Leukocytes, Mononuclear / chemistry
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Mouth Mucosa / chemistry
  • Mouth Mucosa / metabolism*
  • Observer Variation
  • Polymerase Chain Reaction / methods
  • Polymerase Chain Reaction / standards*
  • Reproducibility of Results
  • Saliva / chemistry
  • Saliva / metabolism*
  • Salivary alpha-Amylases / genetics*

Substances

  • DNA
  • AMY1A protein, human
  • Salivary alpha-Amylases

Grants and funding

Funding source of the project: SICS core funding of Yung Seng Lee (C8019). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.