We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genome sequencing of human in vitro fertilisation embryos for pathogenic variation screening.
- Authors
Murphy, Nicholas M.; Samarasekera, Tanya S.; Macaskill, Lisa; Mullen, Jayne; Rombauts, Luk J. F.
- Abstract
Whole-genome sequencing of preimplantation human embryos to detect and screen for genetic diseases is a technically challenging extension to preconception screening. Combining preconception genetic screening with preimplantation testing of human embryos facilitates the detection of de novo mutations and self-validates transmitted variant detection in both the reproductive couple and the embryo's samples. Here we describe a trio testing workflow that involves whole-genome sequencing of amplified DNA from biopsied embryo trophectoderm cells and genomic DNA from both parents. Variant prediction software and annotation databases were used to assess variants of unknown significance and previously not described de novo variants in five single-gene preimplantation genetic testing couples and eleven of their embryos. Pathogenic variation, tandem repeat, copy number and structural variations were examined against variant calls for compound heterozygosity and predicted disease status was ascertained. Multiple trio testing showed complete concordance with known variants ascertained by single-nucleotide polymorphism array and uncovered de novo and transmitted pathogenic variants. This pilot study describes a method of whole-genome sequencing and analysis for embryo selection in high-risk couples to prevent early life fatal genetic conditions that adversely affect the quality of life of the individual and families.
- Subjects
NUCLEOTIDE sequencing; FERTILIZATION in vitro; EMBRYOS; PREIMPLANTATION genetic diagnosis; GENE amplification; TANDEM repeats
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-60704-0