Validation of fetus aneuploidy in 221 Korean clinical samples using noninvasive chromosome examination: Clinical laboratory improvement amendments-certified noninvasive prenatal test.
- Author:
Min Jeong KIM
1
;
Chang Hyuk KWON
;
Dong In KIM
;
Hee Su IM
;
Sungil PARK
;
Ji Ho KIM
;
Jin Sik BAE
;
Myunghee LEE
;
Min Seob LEE
Author Information
- Publication Type:Original Article
- Keywords: Prenatal diagnosis; High-throughput nucleotide sequencing; Computational biology; Cell-free DNA; Trisomy; Aneuploidy
- MeSH: Aneuploidy*; Computational Biology; DNA; Fetus*; Genome; High-Throughput Nucleotide Sequencing; Humans; Prenatal Diagnosis; Trisomy
- From:Journal of Genetic Medicine 2015;12(2):79-84
- CountryRepublic of Korea
- Language:English
- 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.
