Validation of fetus aneuploidy in 221 Korean clinical samples using noninvasive chromosome examination: Clinical laboratory improvement amendments-certified noninvasive prenatal test

Min-Jeong Kim; Chang Hyuk Kwon; Dong-In Kim; Hee Su Im; Sungil Park; Ji Ho Kim; Jin-Sik Bae; Myunghee Lee; Min Seob Lee

doi:10.5734/JGM.2015.12.2.79

J Genet Med 2015;12:79-84

Published online December 31, 2015; https://doi.org/10.5734/JGM.2015.12.2.79

Min-Jeong Kim, Chang Hyuk Kwon, Dong-In Kim, Hee Su Im, Sungil Park, Ji Ho Kim, Jin-Sik Bae, Myunghee Lee, and Min Seob Lee^*

Eone-Diagnomics Genome Center (EDGC), Inc., Incheon, Korea

Min Seob Lee, Ph.D. Eone-Diagnomics Genome Center (EDGC), Inc., 291 Harmony-ro, Yeonsu-gu, Incheon 22014, Korea. Tel: +82-32-210-2341, Fax: +82-32-210-2349, E-mail: mlee@edgc.com

Received November 11, 2015; Revised December 14, 2015; Accepted December 24, 2015.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract: Purpose:
We developed and validated a fetal trisomy detection method for use as a noninvasive prenatal test (NIPT) including a Clinical Laboratory Improvement Amendments (CLIA)-certified bioinformatics pipeline on a cloud-based computing system using both Illumina and Life Technology sequencing platforms for 221 Korean clinical samples. We determined the necessary proportions of the fetal fraction in the cell-free DNA (cfDNA) sample for NIPT of trisomies 13, 18, and 21 through a limit of quantification (LOQ) test.
Materials and Methods:
Next-generation sequencing libraries from 221 clinical samples and three positive controls were generated using Illumina and Life Technology chemistries. Sequencing results were uploaded to a cloud and mapped on the human reference genome (GRCh37/hg19) using bioinformatics tools. Based on Z-scores calculated by normalization of the mapped read counts, final aneuploidy reports were automatically generated for fetal aneuploidy determination.
Results:
We identified in total 29 aneuploid samples, and additional analytical methods performed to confirm the results showed that one of these was a false-positive. The LOQ test showed that the proportion of fetal fraction in the cfDNA sample would affect the interpretation of the aneuploidy results.
Conclusion:
Noninvasive chromosome examination (NICE), a CLIA-certified NIPT with a cloud-based bioinformatics platform, showed unambiguous success in fetus aneuploidy detection.; Keywords : Prenatal diagnosis, High-throughput nucleotide sequencing, Computational biology, Cell-free DNA, Trisomy, Aneuploidy