Clinically validated whole genome screening for embryos

Demonstrating high concordance in exome calls and accurately detecting de novo variants and variants linked to autosomal recessive conditions without the use of probes, PGT-WGS emerges as an invaluable tool for prospective parents

Before implantation subsequent to in vitro fertilization (IVF), the current options for Preimplantation Genetic Testing (PGT) are PGT for Aneuploidy (PGT-A) and, if clinically indicated, PGT for monogenic conditions (PGT-M). A more comprehensive approach involves PGT whole genome sequencing (PGT-WGS). PGT-WGS incorporates PGT-A, screens for hundreds of monogenic conditions, and can evaluate polygenic risk. Here we compare PGT-WGS results against the genome of the subsequently born child. We demonstrated high levels of concordance (both in sensitivity and precision) in exome variant calls between amplified embryonic DNA and sequenced fetal cord blood. This concordance was higher when filtering against 1300 targeted monogenic conditions implicated in birth defects, neurodevelopmental disorders, and hereditary cancer. To evaluate PGT-WGS’s ability to identify de novo variants we compared the child’s genome to parental genomes and demonstrated that PGT-WGS successfully identified 5/5 confirmed de-novo variants. We further demonstrated concordance in polygenic risk scores calculated for both the embryo and the subsequently born child. This agreement extended to both traditional polygenic scores and oligogenic scores (Type 1 diabetes, Celiac disease, and Alzheimer’s Disease), which heavily rely on accurate genotyping of HLA and APOE sites. To our knowledge, this is the first direct concordance study between a whole-genome sequencing of a trophectoderm biopsy and the DNA of the subsequently born child. By demonstrating a high degree of whole-exome concordance and adept detection of de novo variants, this approach showcases PGT-WGS’s capability to identify genetic variants not explicitly targeted for monogenic screening.

Whole genome embryo screening provides a solution for mitigating the risk of monogenic diseases among patients facing challenging scenarios where traditional PGT for monogenic conditions falls short

PGT-WGS successfully identified monogenic disease in embryos with significant clinical implications, without the need for prior information from the IVF center or the use of PGT-M probes. PGT-WGS emerges as a valuable tool in identifying unsuspected familial risk and preventing the transmission of genetic disorders during IVF cycles

Before implantation subsequent to in vitro fertilization (IVF), the current options for Preimplantation Genetic Testing (PGT) are PGT for Aneuploidy (PGT-A) and, if clinically indicated, PGT for monogenic conditions (PGT-M). A more comprehensive approach involves PGT whole genome sequencing (PGT-WGS). PGT-WGS incorporates PGT-A, screens for hundreds of monogenic conditions, and can evaluate polygenic risk. Here we compare PGT-WGS results against the genome of the subsequently born child. We demonstrated high levels of concordance (both in sensitivity and precision) in exome variant calls between amplified embryonic DNA and sequenced fetal cord blood. This concordance was higher when filtering against 1300 targeted monogenic conditions implicated in birth defects, neurodevelopmental disorders, and hereditary cancer. To evaluate PGT-WGS’s ability to identify de novo variants we compared the child’s genome to parental genomes and demonstrated that PGT-WGS successfully identified 5/5 confirmed de-novo variants. We further demonstrated concordance in polygenic risk scores calculated for both the embryo and the subsequently born child. This agreement extended to both traditional polygenic scores and oligogenic scores (Type 1 diabetes, Celiac disease, and Alzheimer’s Disease), which heavily rely on accurate genotyping of HLA and APOE sites. To our knowledge, this is the first direct concordance study between a whole-genome sequencing of a trophectoderm biopsy and the DNA of the subsequently born child. By demonstrating a high degree of whole-exome concordance and adept detection of de novo variants, this approach showcases PGT-WGS’s capability to identify genetic variants not explicitly targeted for monogenic screening.