Single-cell DNA sequencing reveals a high incidence of chromosomal abnormalities in human blastocysts

Effrosyni A. Chavli*, Sjoerd J. Klaasen, Diane Van Opstal, Joop S.E. Laven, Geert J.P.L. Kops*, Esther B. Baart*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aneuploidy, a deviation from the normal chromosome copy number, is common in human embryos and is considered a primary cause of implantation failure and early pregnancy loss. Meiotic errors lead to uniformly abnormal karyotypes, while mitotic errors lead to chromosomal mosaicism: the presence of cells with at least 2 different karyotypes within an embryo. Knowledge about mosaicism in blastocysts mainly derives from bulk DNA sequencing (DNA-Seq) of multicellular trophectoderm (TE) and/or inner cell mass (ICM) samples. However, this can only detect an average net gain or loss of DNA above a detection threshold of 20%–30%. To accurately assess mosaicism, we separated the TE and ICM of 55 good-quality surplus blastocysts and successfully applied single-cell whole-genome sequencing (scKaryo-Seq) on 1,057 cells. Mosaicism involving numerical and structural chromosome abnormalities was detected in 82% of the embryos, in which most abnormalities affected less than 20% of the cells. Structural abnormalities, potentially caused by replication stress and DNA damage, were observed in 69% of the embryos. In conclusion, our findings indicated that mosaicism was prevalent in good-quality blastocysts, whereas these blastocysts would likely be identified as normal with current bulk DNA-Seq techniques used for preimplantation genetic testing for aneuploidy.

Original languageEnglish
Article numbere174483
JournalJournal of Clinical Investigation
Volume134
Issue number6
DOIs
Publication statusPublished - 15 Mar 2024

Fingerprint

Dive into the research topics of 'Single-cell DNA sequencing reveals a high incidence of chromosomal abnormalities in human blastocysts'. Together they form a unique fingerprint.

Cite this