RT Journal Article
SR Electronic
T1 Genome-Wide Disease Screening in Early Human Embryos with Primary Template-Directed Amplification
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.06.451077
DO 10.1101/2021.07.06.451077
A1 Xia, Yuntao
A1 Gonzales-Pena, Veronica
A1 Klein, David J
A1 Luquette, Joe J
A1 Puzon, Liezl
A1 Siddiqui, Noor
A1 Reddy, Vikrant
A1 Park, Peter
A1 Behr, Barry R
A1 Gawad, Charles
YR 2021
UL http://biorxiv.org/content/early/2021/08/30/2021.07.06.451077.abstract
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.