Poster #88: Mahek Virani

Identifying Risk and Protective Genetic Variants for Human Embryo Aneuploidy Using Whole-Genome Sequencing from Preimplantation Genetic Testing

Mahek Virani1,2, LouiseCastillo3, Manuel Viotti3, Jinchuan Xing1,2 1 Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. 2 Human Genetics Institute of New Jersey, Rutgers, The State University of New Jersey, Piscataway, NJ, USA. 3 Kindlabs, Kindbody, New York, NY, USA.

Aneuploidy, having one or more missing or extra chromosomes, is frequently detected in human embryos as a major cause of early pregnancy loss and often results in implantation failure, miscarriage, and congenital defects. Maternal age is an important risk factor for aneuploidy, however, significant variations have been found within individuals of the same age. Previous studies show that genetic variants also contribute to aneuploidy risk by altering chromosome segregation during meiosis in eggs and during mitosis in embryos. This study aims to identify genetic variants that contribute to egg aneuploidy risk in humans using DNA from the preimplantation genetic testing for aneuploidy (PGTA) done on blastocysts from IVF patients. Patients with a relatively high aneuploidy rate and an oocyte age of < 35 years were considered the risk group and patients with a low aneuploidy rate and an oocyte age of ≥ 38 years were considered the protective group. Whole–genome-amplified PCR products originally used for PGTA were whole genome sequenced. A BWA + GATK pipeline was used to identify genomic variants. Variant annotation was performed using Ensembl Variant Effect Predictor. These annotations add information on functional consequences, allele frequencies from gnomAD, and other predictive factors. Filtering was done based on population frequency and impact to prioritize variants for further investigation. Of the genes that contain the prioritized variants, those with higher variant occurrence across samples and known implications in infertility and aneuploidy were selected for further investigation, including pathway analysis and literature review. Candidate genes identified in this study will be tested in a mouse oocyte in vitro system for functional impact to validate these findings further. Ultimately, this will contribute to the current knowledge on aneuploidy and shed light on risk and protective factors with the potential to improve testing and treatment.