Constitutional and mosaic CNVs in families with reproductive losses

It is known that the placenta of human embryos in the I trimester of pregnancy and fetuses in the II and III trimesters are enriched with CNVs. This property is assumed to be necessary for the normal functioning of placenta and successfull pregnancy. At the same time, pathogenic CNVs associated with known microdeletion and microduplication syndromes were detected in placentas of spontaneous abortions (SA). However, these data were obtained on DNA isolated from the mixture of placental cells, while placental tissues in I trimester can be divided into chorionic villi (CV) and extraembryonic mesoderm (EM), originating from different germ layers. The study of two tissues allows tracking the distribution of CNVs in the placenta, identifying de novo variants that arose after the separation of germ layers, and, in the presence of parental DNA, identifying inherited CNV. Here, for the first time, CV and EM (34 SA), as well as parental DNA (17 couples) were studied on Agilent 180K microarrays. CNVs were detected in one or both tissues in 21 (62%) SA. A total of 226 variations were identified, of which 126 (56%) were detected in one of the tissues (75 in CV (33%) and 51 in EM (23%)); at the same time, 100 CNVs (44%) were present in both tissues. In CV, the variants were found 1.5 times more often than in EM. The ratio of de novo and inherited CNVs was 3:1. Pathogenic and likely pathogenic variations were present either in both tissues or only in CV.

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