Noninvasive prenatal detection of chromosomal aneuploidies using different next generation sequencing strategies and algorithms

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Abstract
Objective Here we describe the successful application of massively parallel sequencing for noninvasive prenatal detection of trisomy 21. In addition, for the detection of a broader spectrum of fetal aneuploidies, a target enrichment approach was successfully tested. Methods The circulating cell‐free DNA was prepared from 53 maternal blood samples and analysed using Illumina's sequencing systems Genome AnalyzerIIx and HiSeq2000, respectively. In a first experiment the SureSelect Target Enrichment System was tested. Results In our initial study analysing 42 samples on the Genome AnalyzerIIx, all eight samples from women carrying a trisomy 21 fetus were correctly identified. On the basis of our HiSeq2000 sequence data, we discussed new algorithms for detection of fetal trisomy 21. In addition, we successfully used the combination of a target enrichment system followed by sequencing and were able to identify fetal trisomy 13 and fetal trisomy 21. Conclusions Our results confirm previous reports that massively parallel sequencing of cell‐free fetal DNA allows the reliably noninvasive detection of trisomy 21 from maternal blood with the potential to enhance test selectivity and specificity by bioinformatic means. According to our preliminary results, targeted sequencing might be an alternative strategy to detect chromosomal aneuploidies besides trisomy 21. © 2012 John Wiley & Sons, Ltd.