Genetic scientists have used a new technique that allows the whole genome of IVF embryos to be scanned via the cells of 10 biopsies. The researchers say 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.

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The development enables the whole genetic code to be scanned for “potentially dangerous” mutations – but more work is needed to fathom the precise disease consequences.

Published online by the Genome Research journal, the whole-genome sequencing results were analyzed from cell biopsies taken from two individual embryos from the same couple.

The technique means the 5-day-old, blastocyst-stage embryos could be scanned, in a research first, for “de novo mutations” – those arising spontaneously in the egg or sperm and not inherited from either parent.

This, the authors say, increases the power of whole-genome testing to detect the diseases that might befall test-tube babies.

Dr. Brock Peters and Dr. Radoje Drmanac – from Complete Genomics, the company based in Mountain View, CA, that has developed the screening technology – are among the study’s authors. They claim:

This is the first demonstration that a large majority of single-base de novo mutations, which cause a disproportionally high percentage of genetic defects, can be detected in pre-implantation genetic diagnosis.”

In contrast, the pre-implantation genetic diagnosis that is used in fertility clinics can detect only the large chromosomal abnormalities or genetic mutations that are passed on to in vitro-fertilized (IVF) embryos by their 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, Drs. Peters and Drmanac, working with other commercial researchers from Complete Genomics and from Reprogenetics, used the technique at the NYU Fertility Center to remove any falsely identified genetic mutations.

Using their “long fragment read” technology, the researchers used 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.”

Drs. Peters and Drmanac say: “Because each individual carries on average [fewer] than 100 de novo mutations, being able to detect and assign parent of origin for these mutations, which are the cause of many diseases, required this extremely low error rate.”

The study unveiled de novo mutations that “may be potentially damaging” – but the particular health consequences of these remain unclear.

Such a practical limitation to present advances in whole-genome sequencing is a theme, along with ethical concerns, running through the other recent developments selected below.

In one embryo in the study, the researchers 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 ZNF266 and SLC26A10 genes that may be potentially damaging.

“The biggest hurdle now is one of how to analyze the medical impact of detected mutations and make decisions based on those results,” say Drs. Peters and Drmanac.

The authors conclude their paper by saying their results suggest that:

Whole-genome sequencing using barcoded DNA could be used in the future as part of the pre-implantation genetic diagnosis process to maximize comprehensiveness in detecting disease-causing mutations and reduce the incidence of genetic diseases.”

Advances such as these continue to be brought to IVF technology, which overcame a major ethico-legal hurdle this month when members of the UK’s parliament voted overwhelming in favor of potential new laws in the country to allow the creation of IVF embryos with mitochondrial DNA from a third donor.

In addition to the nuclear DNA coming from an embryo’s two parents, a small amount of DNA would also come from a third “parent.”

This DNA would affect only the tiny “power stations” within cells, the mitochondria, and would not pass on any familial genetic traits from the third donor.

The technique would enable couples to use IVF for the conception of children who otherwise would have inherited devastating mitochondrial diseases. See: Three-parent embryos approved in UK.

Falling cost and improving reliability mean the idea of whole-genome sequencing (WGS) has become a real prospect for everyday diagnostic use in addition to the power given to genetic research.

But should WGS be used as a part of screening programs for newborn babies?

All the genetic code would be read, so the testing would not be confined to the targeted detection of certain diseases, as happens now – for example, to pick up sickle cell disease or cystic fibrosis.

McGill University researchers raised concerns about this in a journal article last March, saying that the availability of whole-genome sequencing was “likely to change the practice of population screening programs such as newborn screening.”

They raised key ethical, legal and social issues that “need to be weighed carefully.” See more about this story: Newborn screening: should whole-genome sequencing be introduced?

While the recent pace of improvements in whole-genome sequencing have raised the prospects of wider DNA screening, further development is needed before everyday relevance in clinical practice can be achieved, as is the case for the latest study.

For example, in a study published last March, for 12 adult volunteers who had undergone whole-genome sequencing the clinicians could not agree on the practical meaning of genetic variations detected. See: Whole-genome sequencing ‘not ready for widespread clinical use’.