A next-generation sequencing method for gene doping detection that distinguishes low levels of plasmid DNA against a background of genomic DNA

Gene Ther. 2019 Aug;26(7-8):338-346. doi: 10.1038/s41434-019-0091-6. Epub 2019 Jul 11.

Abstract

Gene doping confers health risks for athletes and is a threat to fair competition in sports. Therefore the anti-doping community has given attention on its detection. Previously published polymerase chain reaction-based methodologies for gene doping detection are targeting exon-exon junctions in the intron-less transgene. However, because these junctions are known, it would be relatively easy to evade detection by tampering with the copyDNA sequences. We have developed a targeted next-generation sequencing based assay for the detection of all exon-exon junctions of the potential doping genes, EPO, IGF1, IGF2, GH1, and GH2, which is resistant to tampering. Using this assay, all exon-exon junctions of copyDNA of doping genes could be detected with a sensitivity of 1296 copyDNA copies in 1000 ng of genomic DNA. In addition, promotor regions and plasmid-derived sequences are readily detectable in our sequence data. While we show the reliability of our method for a selection of genes, expanding the panel to detect other genes would be straightforward. As we were able to detect plasmid-derived sequences, we expect that genes with manipulated junctions, promotor regions, and plasmid or virus-derived sequences will also be readily detected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Doping in Sports / methods*
  • Erythropoietin / genetics
  • Erythropoietin / metabolism
  • Exons
  • Genetic Testing / methods*
  • Genetic Testing / standards
  • Genome, Human
  • High-Throughput Nucleotide Sequencing / methods*
  • High-Throughput Nucleotide Sequencing / standards
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Plasmids / genetics*
  • Plasmids / metabolism
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*
  • Sequence Analysis, DNA / standards
  • Transgenes*

Substances

  • Intercellular Signaling Peptides and Proteins
  • Erythropoietin