Poster #76 - Weijun Zeng

Identifying maternal risk and protective genes for egg aneuploidy

Weijun Zeng, Karen Schindler, Jinchuan Xing

Egg aneuploidy is a major cause of female infertility, but how intrinsic oocyte aging interacts with the genetic risk of egg aneuploidy is still not well understood. Whole-exome sequencing (WES) data from IVF patients with higher or lower than normal age-adjusted aneuploidy rates is used to identify hundreds of candidate genes that may affect meiotic function. To place these findings into the biological context of reproductive aging, we compared these candidate genes with Differential Expression Genes (DEGs) from single-oocyte RNA-seq data from young and old oocyte. We identified 3 DEGs that are up-regulated in aged oocyte and overlapped with patient-derived risk genes, pointing to intrinsic aging processes such as weakened spindle assembly checkpoints. On the other hand, 3 genes from patients with low age-adjusted egg aneuploidy rate overlapped DEGs that are upregulated in young vs aged oocyte suggest that variants in these genes might provide protective aging-related defects. Together, these results demonstrate the value of integrating patient genomics with functional transcriptomics to uncover drivers of aneuploidy risk and reproductive aging.