| HRA000332
(Controlled Access)
|
The discovery of embryonic cell-free DNA (cfDNA) in spent embryo culture media (SEM) has brought hope for the noninvasive preimplantation genetic testing. However, the cellular origins of SEM cfDNA are not sufficiently understood and methods for determining maternal DNA contamination are limited. Here, we performed whole-genome DNA methylation sequencing for SEM cfDNA (n = 194). Our results demonstrated that SEM cfDNA were derived from blastocysts, cumulus cells and polar bodies. We identified the cumulus-specific differentially methylated regions (C-DMRs, n = 769) and the oocyte/polar body-specific DMRs (O-DMRs, n = 548), and established an algorithm for deducing the cumulus, the polar body and the net maternal DNA contamination ratios in SEM. We showed that DNA methylation sequencing accurately detected chromosome aneuploidy in SEM, and by integrating the origin analysis, it distinguished SEM samples between low and high false negative rate (FNR) and gender discordance rate (GDR). |
