The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform

PLoS One. 2014 Oct 20;9(10):e110240. doi: 10.1371/journal.pone.0110240. eCollection 2014.

Abstract

Objective: Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton.

Methods: From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China). Adapter-ligated DNA libraries were analyzed by the Ion Proton™ System (Life Technologies, Grand Island, NY, USA) with an average 0.3× sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection.

Results: Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21.

Conclusion: These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosomes, Human, Pair 18 / genetics
  • Down Syndrome / diagnosis*
  • Down Syndrome / genetics
  • Feasibility Studies
  • Female
  • Fetus*
  • High-Throughput Nucleotide Sequencing / instrumentation*
  • Humans
  • Male
  • Predictive Value of Tests
  • Pregnancy
  • Prenatal Diagnosis / instrumentation*
  • Semiconductors*
  • Sequence Analysis, DNA / instrumentation*
  • Trisomy / diagnosis*
  • Trisomy / genetics
  • Trisomy 18 Syndrome
  • Young Adult

Associated data

  • SRA/SRP044689

Grants and funding

This work was supported by the Industrial Strategic Technology Development Program, 10040231, ‘Bioinformatics platform development for next generation bioinformation analysis’ funded by the Ministry of Knowledge Economy (MKE, Korea). Co-authors Young Joo Jeon, Sin-Gi Park, Hee Jae Joo, and Jong Bhak are employed by TheragenEtex Bio Institute. TheragenEtex Bio Institute provided support in the form of salaries for authors YJJ, SGP, HJJ, and JB, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Co-authors Young Joo Jeon, Sin-Gi Park, Hee Jae Joo, and Jong Bhak are employed by Genome Care. Genome Care provided support in the form of salaries for authors YJJ, SGP, HJJ, and JB, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Co-authors Shengmao Quan, Ahong Zhang, Hailing Zheng, Xingqiang Zhu, Jin Lin, Huan Xu, and Hongliang Chen are employed by Xiamen Vangenes BioTech. Xiamen Vangenes BioTech provided support in the form of salaries for authors SQ, AZ, HZ, XZ, JL, HX, and HC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Co-author Byung Chul Kim is employed by Clinomics. Clinomics provided support in the form of salaries for author BCK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contributions’ section.