Whole-genome sequencing detects de novo mutations in embryos

Scientists have shown for the first time that whole-genome sequencing (WGS) in IVF embryos can detect 'de novo' mutations. 

'These findings are a significant step in developing advanced whole-genome sequencing as the "ultimate" screen to find the healthiest embryos through PGD [preimplantation genetic diagnosis],' said Dr Santiago Munné, study author and director of genetics laboratory Reprogenetics.

'This new approach can detect almost all genome variation, which may eliminate the need for further genetic testing during pregnancy or after birth while ensuring selection of the healthiest embryo for transfer to the future mother.'

In the study, published in Genome Research, the researchers used a technique called 'advanced massively parallel WGS' on three five- to ten-cell biopsies from two blastocyst-stage embryos. They were able to sequence over 95 percent of the genome and to detect up to 82 percent of de novo mutations. 

One hindrance to using WGS in embryos is that the process of DNA amplification during the procedure results in thousands of mutations which cannot be told apart from true de novo mutations present in the embryo. But by using another technology, called long fragment read, which allowed them to sift out mutations arising during amplification, the false-positive rate was equivalent to less than ten errors per embryo.

The fact that 'de novo mutations can be detected with such high sensitivity and an exceptionally low error rate using so few embryonic cells is remarkable,' said lead investigator Dr Brock Peters of Complete Genomics.

De novo mutations are not inherited from either parent but arise spontaneously in the sperm and egg. They are disproportionally linked to various genetic diseases and may lead to severe intellectual disabilities, autism and epileptic encephalopathies.

The authors say that one of the main challenges remaining will be to interpret the detected mutations in terms of their clinical consequences and how to use the results in decision-making. However, they hope that in time, when the costs and duration of the technique are both reduced, it will become a standard procedure during IVF.

'Additional clinical studies with many more samples are required to further demonstrate the promises of this type of analysis for preimplantation genetic diagnosis,' they note.