Whole Genetic Code of IVF Embryos Scanned for Mutations

Currently, the methods available for preimplantation genetic diagnosis (PGD) of in vitro fertilized (IVF) embryos do not detect de novo single-nucleotide and short indel mutations, which have been shown to cause a large fraction of genetic diseases.

The detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing has been accomplished and the technique would enable couples to use IVF for the conception of children who otherwise would have inherited devastating mitochondrial diseases.


Genomic scientists at Complete Genomics, Inc. (Mountain View, CA, USA) and their colleagues used a new technique that allows the whole genome of IVF embryos to be scanned via the cells of 10 biopsies. The team said the testing is the first to be able to detect all the new genetic mutations that happen uniquely in an individual, as opposed to only those that have been handed down from parents.

Using up to just 10 cells to do the whole-genome sequencing means the DNA has to be amplified, which can introduce errors. However, the scientists working with another commercial team from Reprogenetics (Livingston, NJ, USA), used the technique at a fertility center to remove any falsely identified genetic mutations. They applied their "long fragment read" technology, using DNA barcodes to assign DNA fragments to the embryos' maternal or paternal genome. They were able to remove over 100,000 sequencing errors, reducing the error rate approximately 100-fold over previous studies.

The technique means the 5-day-old, blastocyst-stage embryos could be scanned for de novo mutations, those arising spontaneously in the egg or sperm and not inherited from either parent. In one embryo in the study, the scientists did not find any de novo mutations in the regions of the genome that code for proteins. In the other embryo from the couple, however, they picked up two coding mutations in the zinc finger protein 266 (ZNF266) and the solute carrier family 26, (SLC26A10) genes that may be potentially damaging.

The authors concluded that the biggest hurdle now is one of how to analyze the medical impact of detected mutations and make decisions based on those results. Whole-genome sequencing using barcoded DNA could be used in the future as part of the preimplantation genetic diagnosis process to maximize comprehensiveness in detecting disease-causing mutations and reduce the incidence of genetic diseases. The study was published on February 11, 2015, in the journal Genome Research.

Related Links:
Complete Genomics, Inc.
Reprogenetics