In 2008 two research groups have independently shown in proof of concept publications that trisomy 21 can be detected by high-throughput sequencing of cell free fetal DNA from the mother’s blood plasma with high specificity and high level of sensitivity (Fan et al., 2008; Chiu et al., 2008).
In short, Illumina reads are mapped to the reference human genome and by counting the reads that map to each chromosome the relative dosage of each chromosome is measured. In case of trisomy 21 or other aneuploidies the relative dosage of the affected chromosome is statistically overrepresented in the data set.
Within the last two months the companies Sequenom (Ehrich et al., 2011) and Verinata Health (Sehnert et al., 2011) both have published studies examining large test sets of patients. Both companies apply sequencing on GAIIx. The approaches mostly differ in normalization of sequencing data and bioinformatics analysis. Using a smart algorithm for normalizing the chromosome-counting data Verinata Health was able to classify 100 % correct all trisomy 21 and trisomy 18 samples in the test set (Sehnert et al., 2011).
While Sequenom recently finished the Clinical Validation Studies (GenomeWeb and Sequenom’s Web Page), Verinata Health is currently conducting a blinded clinical study to further demonstrate the diagnostic accuracy of their method (Sehnert et al., 2011)
Current screening methods are usually showing high false-positive results. Only invasive methods with high risk for mother and fetus provide definite genetic information about the fetus. The NGS based detection of fetal aneuploidy in high-risk-pregnancies is very promising from my point of view, as the method is non-invasive and is so far displaying high sensitivity and specificity.