Advancements and Applications of Preimplantation Genetic Testing in In Vitro Fertilization: A Comprehensive Review

DNA Sequencing Advances Expand Genetic Test Options For Would-be Parents

Next-generation DNA sequencing helps screen more people for more inherited genetic disorders.Credit: KTSDesigns/SPL/Getty Images

Technology to test for genes that can cause disease has improved to the point that screening programmes to detect disease-causing genes in would-be parents should be significantly expanded to improve public health. That's the view of an expert panel assembled by the American College of Medical Genetics (ACMG).

At present, such 'carrier screening' is offered routinely only to women in ethnic and racial groups at risk for hereditary conditions, including sickle cell disease in the Black population and Tay-Sachs disease in the Ashkenazi Jewish population. But the ACMG's Professional Practice and Guidelines Committee has recommended that all pregnant women – regardless of their ethnic background – be offered tests for the genes that cause at least 113 of the most common hereditary conditions.

Such pan-ethnic carrier screening would offer more equitable access to care and assessments of women's risk of having a child with a genetic disorder. This in turn would allow them to make a more informed choice before conception or give them more options about how to proceed with a pregnancy.

The ACMG recommendation to expand carrier screening aligns with the findings published in June by a separate group of medical genetics experts from medical centres, disease foundations, genetic testing laboratories and insurance companies. The group emphasizes the benefits of pan-ethnic carrier screening for people who carry such genes.

Although the goals of carrier screening have not changed, the technology used has changed dramatically, the ACMG committee writes. "Whereas in prior years, carrier screening was a scarce resource reserved only for those with the highest risk, a more attainable price point now allows for the opportunity to reach every patient."

Powerful tool

A key to that more attainable price point is next-generation sequencing, which is faster and more powerful than earlier DNA-sequencing methods because it breaks DNA into fragments and sequences the nucleotides simultaneously. Researchers have used next-generation sequencing since the mid-2000s, but genetic testing laboratories began adopting it more recently. Today, numerous genetic testing laboratories offer the service.

Nevertheless, clinicians do not routinely offer expanded carrier screening to their patients, says medical geneticist Susan Klugman of the Albert Einstein College of Medicine, a committee member. This may be due in part to a lack of demand. "Some [women] say they don't need testing because there's nothing in their history," she says. But they may be surprised to learn that they are a carrier for an autosomal disorder.

"The consequences of having an affected pregnancy are life-changing," says Dagan Wells, who directs Oxford University's preimplantation genetic diagnosis laboratory. "You might prefer to be aware of that risk to make reproductive choices."

To give his patients that option, Wells has expanded carrier screening options in his clinic. Couples seeking assistance in reproduction are screened before implantation, and gamete donors are tested too. Patients can then choose donor gametes that don't have overlapping mutations. "The use of expanded carrier screening is becoming very common in that particular area," Wells says.

It's growing in other areas as well, and it's not hard for patients to understand why it might be wise. "Eighty percent of couples who have an affected child never knew they were carriers of a recessive condition," Wells says. That makes expanded carrier screening an insurance policy, he adds. "You take it out with the hope that it won't be relevant."

Explore how next-generation sequencing can empower pan-ethnic carrier screening here.

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