A procedure used in preconception diagnosis can lead to problems with pregnancies

April 7, 2011

A new study demonstrates that a procedure used in preconception diagnosis to identify eggs that are free of genetic disease might not work well in all cases. The research, published by Cell Press in the April issue of the American Journal of Human Genetics, highlights the issues associated with analyzing the amount of mutant mitochondrial DNA in supporting cells as a proxy for eggs prior to in vitro fertilization.

Preimplantation genetic diagnosis (PGD) and preconception diagnosis (PCD) are services that have been very useful to couples who have a genetic defect in their family. "PGD and PCD represent alternatives to conventional prenatal diagnosis for couples who have a high risk of giving birth to a child affected with a serious … and can prevent the anxiety associated with a prenatal diagnosis procedure and the optional termination of the pregnancy," explains lead study author Dr. Julie Steffann from the Université Paris-Descartes and Hôpital Necker-Enfants Malades in Paris, France. The processes involve performing genetic diagnostics on a cell removed from a developing embryo, in the case of PGD, or from a cell called a polar body, which supports the unfertilized egg, in the case of PCD. Those embryos and eggs that are found to be free of mutations are then considered safe to proceed with through pregnancy.

Dr. Steffann and colleagues Nadine Gigarel, and Jean-Paul Bonnefont, and Arnold Munnich from the Université Paris-Descartes and Hôpital Necker-Enfants Malades and David Samuels from Vanderbilt University Medical Center in Nashville, TN show that assuming the polar body has a genetic make-up that matches that of the unfertilized egg can be complicated in some cases. The polar body divides from the egg when the egg develops, so it was thought that it could serve as a proxy for the egg and that testing it would allow a genetic diagnosis to be made without harming the egg. This is true for genes in the nuclear DNA, but the authors show that things are different for genes in the mitochondria.

If a person has a mutation in mitochondrial DNA, it can be present in all of the mitochondria or in a percentage of the mitochondria. This is referred to as mutant load. If the mutant load is high, the person can have the disease associated with that mutation, but if the mutant load is low enough, the person can be healthy. For these reasons, clinicians performing PCD want to select eggs with a low mutant load. In this work, Dr. Steffann and colleagues show that there is a poor correlation between the mutant load of in an egg and that of its polar body. Finding a low mutant load in a polar body doesn't mean that the mutant load will be low in the associated egg; this could lead to incorrect conclusions regarding which eggs are safe to use for pregnancy.

"Our findings argue against the use of the polar body as a diagnostic material for mtDNA disorders, unless the purpose is for the selection of embryos that are completely mutation free," concludes Dr. Steffann. "Indeed, all mutation-free polar bodies were found to be associated with mutation-free eggs. Unfortunately, because the number of mutation-free is low in women who have mtDNA mutations, the PCD option would dramatically decrease the successful pregnancy rate."

Related Stories

Recommended for you

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

Discovering a protein's role in gene expression

November 10, 2017
Northwestern Medicine scientists have discovered that a protein called BRWD2/PHIP binds to histone lysine 4 (H3K4) methylation—a key molecular event that influences gene expression—and demonstrated that it does so via ...

Twin study finds genetics affects where children look, shaping mental development

November 9, 2017
A new study co-led by Indiana University that tracked the eye movement of twins finds that genetics plays a strong role in how people attend to their environment.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.