Application of high-throughput sequencing in noninvasive detection of fetal chromosome aneuploidies

Objective To determine the feasibility and accuracy of detecting the chromosomal aneuploidy of free fetal DNA in maternal plasma by high-throughput sequencing. Methods High-throughput sequencing was applied to analyze the sequence copy numbers of fetal chromosome. Fetal karyotyping was also carried out for the amniocentesis samples. Consistency between the two methods was analyzed statistically. Results Eight cases were detected to be high risk of chromosomal aneuploidy by high-throughput sequencing, among which 6 cases were confirmed by karyotyping (3 cases of 47, XN, + 21, 1 case of 47, XN, + 18, 1 case of 47, XN, + 13, 1 case of 47, XXY, 1 case of 47, XXX), 1 case was confirmed to be mosaic (46, XN[2]/47, XN, + 13[33]/47, XN, + 13, add(15)(P12)[15]). The amniotic fluid cells from the 100 cases were cultured successfully (success rate was 100%). There was consistency between two methods (κ=0.928). The sensibility is 100% and the false positive rate is 1.1%; The specificity is 98.9% and the positive predictive value is 87.5%. Conclusion High-throughput sequencing is an efficient ways to detectfetal chromosomal aneuploidy. Therefore it has a broad application in prenatal diagnosis. Key words: Noninvasive prenatal diagnosis; Aneuploidy; Maternal serum; Free fetal DNA