PT  - JOURNAL ARTICLE
AU  - Xia, Yuntao
AU  - Gonzales-Pena, Veronica
AU  - Klein, David J
AU  - Luquette, Joe J
AU  - Puzon, Liezl
AU  - Siddiqui, Noor
AU  - Reddy, Vikrant
AU  - Park, Peter
AU  - Behr, Barry R
AU  - Gawad, Charles
TI  - Genome-Wide Disease Screening in Early Human Embryos with Primary Template-Directed Amplification
AID  - 10.1101/2021.07.06.451077
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.07.06.451077
4099  - http://biorxiv.org/content/early/2021/08/30/2021.07.06.451077.short
4100  - http://biorxiv.org/content/early/2021/08/30/2021.07.06.451077.full
AB  - Current preimplantation genetic testing (PGT) enables the selection of embryos based on fetal aneuploidy or the presence a small number of preselected disease-associated variants. Here we present a new approach that takes advantage of the improved genome coverage and uniformity of primary template-directed amplification (PTA) to call most early embryo genetic variants accurately and reproducibly from a preimplantation biopsy. With this approach, we identified clonal and mosaic chromosomal aneuploidy, de novo mitochondrial variants, and variants predicted to cause mendelian and non-mendelian diseases. In addition, we utilized the genome-wide information to compute polygenic risk scores for common diseases. Although numerous computational, interpretive, and ethical challenges remain, this approach establishes the technical feasibility of screening for and preventing numerous debilitating inherited diseases.Competing Interest StatementCG is a co-founder and board member of BioSkryb, which is commercializing primary template-directed amplification. NS is a founder of Orchid and BB is a Scientific Advisor to Orchid.