Fig. 4: The fetal cfDNA study reveals parental and meiotic origin of NDJ and homologous recombination associated with aneuploidy.

a–c A T21 case using matched maternal and fetal mixed DNA, which shows homologous recombination. The occurrence of recombinant could be inferred from the presence of two different AF patterns consistent with MI and MII NDJs (a). In the respective amniocytes, homozygous SNPs (BBB or AAA) are detected only in the telomeric but not centromeric region of chr21 consistent with the presence of recombinant (b). At loci where the mother is heterozygous, fetal homozygosity (AAA or BBB) is consistent with MII NDJ. The probability of meiotic errors for each informative locus is plotted (c). When fetal genotype is heterozygous (ABB or AAB), the prior probability for the detectable MI NDJ is 2/3 while that for MII NDJ is 1/3 assuming an equal incidence in MI and MII NDJs. The dashed lines indicate the transition of MI and MII SNP patterns suggesting a crossover. d–f The cfDNA collected from a pregnant woman carrying a T13 fetus shows the recombinant with the respective fetal genomic DNA SNP pattern (e) and probability of meiotic errors (f). The dashed lines show where transition of MI and MII SNP patterns occurs indicating two crossover events. g Percentages of different types of meiotic errors detected. h Percentages of aneuploidy cases with and without detectable recombinants. i The number of crossovers associated with different types of meiosis NDJ. MI maternal meiosis I, MII maternal meiosis II, PI paternal meiosis I, PII paternal meiosis II, NDJ nondisjunction.