Fig. 2: Combined SNP allelic ratio and RD analysis detects fetal chromosomal aberrations.

a Detection of fetal chromosomal disorders involves a combined analysis of SNP AF and RD. Lv1 QC includes monitoring of sufficient RD, FF, multiple gestations, and maternal CNV. Samples passing Lv1 QC are subjected to the RD-based chromosomal analysis. Lv2 QC includes the detection of maternal AOH and calculation of the number of informative loci where the fetus carries a heterozygous allele, and the mother is homozygous. Samples passing both Lv1 and Lv2 QC undergo the SNP AF-based chromosomal analysis. b–g Representative results of common aneuploidies and MMS. Each case contains results of SNP AF (left panel) and SNP coverage (right panel). Shown on panel b–g, chromosome-specific SNP loci are colored in different groups which are spanning mappable regions on chr13, chr18, chr21, and chrX. The SNPs shown for chr22 are those on the critical region associated with DiGeorge syndrome (chr22:17,322,843-21,118,912). The SNPs in the chrRef group include reference SNPs not on chr13, chr18, chr21, chr22, chrX, and chrY (see Materials and methods). A T21 case due to MI NDJ (b). A T21 case due to PI NDJ (c). A T18 case due to MII NDJ (d). A T13 case due to PII NDJ (e). A 22q11.2 microdeletion case with a loss of maternal chr22 segment (f). A 22q11.2 microdeletion case with a loss of paternal chr22 segment (g). h, i The values of sensitivity (h) and PPV (i) are shown by different analytic methods. Bars indicate 95%CI. AF allelic fraction, RD read depth, RD&AF combined analysis for RD and AF, CI confidence interval, PPV positive predictive value, MMS microdeletion and microduplication syndrome, SNP single nucleotide polymorphism, PCA principal component analysis, CAF central allelic fraction, QC quality control, Lv1 level 1, Lv2 level 2, FF fetal fraction.