VeriSeq™ NIPT Solution v2 delivers genome-wide PCR-free performance and paired-end sequencing-based non-invasive prenatal screening

S. Bhatt¹, N. Flowers², D. Vavrek¹, K. Meier¹, T. Kalista¹, C. Deciu¹, S. Duenwald¹, M.D. Pertile³

¹Illumina, Inc, San Diego, CA, USA; ²Victorian Clinical Genetics Services, Parkville, VIC, Australia; ³NIPT, Victorian Clinical Genetics Services, Melbourne, VIC, Australia

Purpose

To evaluate the performance of a highly automated, PCR-free solution for cell-free DNA-based non-invasive prenatal testing (NIPT), VeriSeq™ NIPT Solution v2, in detecting genome-wide fetal chromosomal abnormalities, including partial deletions and duplications.

Method

Frozen plasma samples from pregnant women with gestational age ≥10 weeks were tested using the VeriSeq™ NIPT Solution v2, which has two reporting options: basic and genome-wide analysis. Here, we describe the genome-wide analysis, which reported on common trisomies, sex chromosome aneuploidies and fetal aneuploidies, rare autosomal aneuploidies, and partial deletions and duplications ≥7 Mb. Clinical outcomes based on cytogenetic results or neonatal physical examination were available for all cases.

Result

The study cohort included 2335 samples with a mean gestational age of 10.9 weeks and maternal age of 35.1 years.
Results were reported for 98.8% (2307/2335) of cases, including 2300 singleton and 7 twin pregnancies. In singleton non-mosaic pregnancies, the sensitivity was 99.2% (126/127) for trisomy 21 and 98.3% (291/296) for abnormalities. When including mosaic samples, the sensitivity was 96.4% (133/138) for trisomy 21 and 95.5% (318/333) for abnormalities. Specificity including mosaicism was 99.90% (1987/1989) for trisomy 21 and 99.31% (1954/1967) for abnormalities, estimates comparable to those excluding mosaicism. In this cohort, there were seven cases of trisomy 21 affecting twins, and chromosome 21 abnormalities were detected in all cases.

In conclusion

The paired-end sequencing-based VeriSeq™ NIPT Solution v2, with basic and genome-wide reporting options, demonstrated high sensitivity and specificity with low failure rates.
Importantly, the 98.3% specificity for any abnormality is much higher than the approximately 95% specificity for trisomy 21 by serum screening. Thus, this genome-wide NIPT reporting approach increases the proportion of chromosomes.