Making next-generation preconception screening a reality for parents

May 10, 2018, Cell Press
Credit: CC0 Public Domain

For those planning to become parents, advances in sequencing technologies could make preconception carrier screening more useful by looking at a much broader set of genes. And in a recent clinical study published May 10 in The American Journal of Humans Genetics, researchers at Oregon Health & Science University found that parents-to-be do want access to the information this kind of screening makes possible. The study uncovered genetic variants that more targeted panels might have missed, but the researchers believe interpretation challenges remain before this technology becomes more broadly available.

Carrier screening has, in the past, focused on looking for genetic variants associated with common disorders, especially those known to be more prevalent in specific ethnic populations. But the development of accurate sequencing technologies that can process data on many genes in parallel has made it feasible and affordable to expand this screening to include much more of the genome.

"By using whole-genome sequencing, we're casting a very large net over a lot of different clinical conditions. We're looking at hundreds of genes, not just a handful of genes or targeted panels, which means this method provides much more information," says senior researcher Sue Richards, a geneticist at Oregon Health and Science University.

Part of the study, which included 131 women who were not yet pregnant and—if those women were found to be carriers—their male partners, looked at how much of that information participants wanted. If they were carriers for a life-threatening disorder, they were automatically informed. But they were also asked to decide what other information they wanted to receive. Richards and her colleagues found that 93% of participants wanted to know if they were carriers for any kind of disorder, whether mild, severe, adult-onset, or unpredictable, and 99% of participants wanted to know about medically actionable findings that might affect their own health. "This tells us that people like to make choices. They wanted information," she says.

The researchers found that 78% of participants were carriers of at least one of the more than 700 disorders for which they were tested. "We found well-known variants in genes that are on other panels. We found ones associated with ultra-rare that aren't on any other panel. We found novel variants, too," she says.

The researchers only informed participants about results for variants that were known to cause a disorder or likely to cause a disorder, which left a large number of what are called variants of uncertain significance. "Those are variants we currently can't interpret at all. And that's the one thing that clinicians hate to see on a clinical lab report. Because it says, 'We can't tell you if this is pathogenic or benign. We don't have enough information,'" she says.

The challenge is even greater in because there's no phenotype to associate with the genetic variant. Carriers are healthy and don't show symptoms, so interpreting a variant that no one knows anything about is much more difficult than doing so in affected individuals. Although there are many groups working on classifying novel variants, Richards still thinks the challenges of interpreting them is one of the biggest roadblocks to making this kind of screening available to everyone. "I think we're pretty close to being there technologically right now. But the other challenges, I think, take a little more time to overcome," she says.

Another challenge, she believes, is helping people understand their results: all participants in her study were provided with extensive genetic counseling, but if this type of becomes more widely offered, a more streamlined counseling process might be necessary.

"Our mission in genetics, and in any medical field, is really to do no harm. This is about empowering people. It's about giving individuals and couples the knowledge that they need to make their own informed decisions and reproductive choices."

Explore further: ACOG recommends use of carrier screening before pregnancy

More information: The American Journal of Human Genetics, Punj et al.: "Preconception Carrier Screening by Genome Sequencing: Results from the Clinical Laboratory" , DOI: 10.1016/j.ajhg.2018.04.004

Related Stories

ACOG recommends use of carrier screening before pregnancy

February 27, 2017
(HealthDay)—The American College of Obstetricians and Gynecologists (ACOG) recommends use of carrier screening for all women, according to two Committee Opinions published in the March issue of Obstetrics & Gynecology.

LRRK2 variants linked to lower age at onset of Parkinson's

November 14, 2017
(HealthDay)—The presence of multiple LRRK2 risk variants is associated with a younger age at onset (AAO) of Parkinson's disease (PD), according to a research letter published online Nov. 13 in JAMA Neurology.

Personal Genome Project Canada study results show promise for health care in Canada

February 5, 2018
First results from the Personal Genome Project Canada, which sequenced the entire personal genomes of 56 healthy participants, suggest whole genome sequencing can benefit health care in Canada, according to results published ...

Phenotype varies for presumed pathogenic variants in KCNB1

August 16, 2017
(HealthDay)—De novo KCNB1 missense and loss-of-function variants are associated with neurodevelopmental disorders, with or without seizures, according to a study published online Aug. 14 in JAMA Neurology.

Expanded prenatal genetic testing may increase detection of carrier status for potentially serious genetic conditions

August 16, 2016
In an analysis that included nearly 350,000 adults of diverse racial and ethnic background, expanded carrier screening for up to 94 severe or profound conditions may increase the detection of carrier status for a variety ...

Gene panels may be useful, cheaper alternative to whole-genome sequencing, study finds

April 14, 2014
As many as 10 percent of women with a personal or family history of breast or ovarian cancer have at least one genetic mutation that, if known, would prompt their doctors to recommend changes in their care, according to a ...

Recommended for you

Scientists identify critical cancer immunity genes using new genetic barcoding technology

October 20, 2018
Scientists at Mount Sinai have developed a novel technology for simultaneously analyzing the functions of hundreds of genes with resolution reaching the single cell level. The technology relies on a barcoding approach using ...

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

Researchers use brain cells in a dish to study genetic origins of schizophrenia

October 16, 2018
A study in Biological Psychiatry has established a new analytical method for investigating the complex genetic origins of mental illnesses using brain cells that are grown in a dish from human embryonic stem cells. Researchers ...

Why heart contractions are weaker in those with hypertrophic cardiomyopathy

October 16, 2018
When a young athlete suddenly dies of a heart attack, chances are high that they suffer from familial hypertrophic cardiomyopathy (HCM). Itis the most common genetic heart disease in the US and affects an estimated 1 in 500 ...


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.