Every baby born in the United States is given a routine blood test to screen for dozens of inherited medical conditions. Now, the U.S. National Institutes of Health is exploring whether to use DNA sequencing to screen newborn babies for additional genetic abnormalities and disorders. Such DNA testing would likely complement, but not replace, the current routine blood tests.
However, before routine genetic screening of infants even approaches reality, many questions need answers, including whether genetic sequencing can accurately identify babies who will develop a disease, according to Dr. Joseph A. Bocchini Jr., chairman of the Advisory Committee on Heritable Disorders in Newborns and Children. The committee evaluates scientific evidence and makes recommendations to the secretary of the Department of Health and Human Services, which in turn provides a recommended uniform screening panel for newborns to the states.
The field is evolving swiftly, Bocchini told CNN: “It’s clear the data is becoming available quite quickly, so potential changes [to the recommended uniform screening panel] may occur within the next few years. But it’s too early to say.”
More clarity is also needed on issues surrounding newborn DNA testing, including consent, accessibility, data privacy and the potential changes to medical practice and costs.
Published Thursday in the American Journal of Human Genetics, one of the several NIH-sponsored scientific studies found that 9.4% of the 159 sequenced babies participating in the research had mutations predictive of a genetic condition or disease.
“The question, though, is: ‘Do we really think that all these babies are going to get sick in the future based on what we found?’ ” said Alan Beggs, co-author of the study and director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital. “And the answer is, ‘Probably not.’ “
What are the current limits to genetic sequencing?
This is the current “dilemma” with genetic testing, said Beggs, this “unknown sensitivity and specificity.” While it may be true, for example, that everyone with a certain illness shares a specific genetic mutation, it may also be true that others also have that mutation, but might never become sick. In genetics, this concept is called “reduced penetrance.”
His study, said Beggs, is really exploring, “How do we best communicate this type of uncertainty to families and to their doctors?”
Another uncertainty with genetic sequencing is that it reveals genes that don’t get “expressed,” meaning the protein the gene codes for doesn’t get made, said Dr. John Lantos, the director of the Children’s Mercy Hospital Bioethics Center in Kansas City, Missouri. “The whole process of going from gene to protein is controlled by all sorts of things we don’t yet understand,” said Lantos, who did not participate in Beggs’ study but conducted his own infant sequencing project for the NIH. “Every attempt to link some specific genome sequence variant with some specific disease runs into all these qualifiers and modifiers and expressivity and penetrance.”
Lantos pointed out that the entire field of genomics is a relative newborn itself.
How is a baby’s genome sequenced?
“The first genome was sequenced in 2003 and cost $3 billion to do,” Lantos recalled. Today, sequencing is “a combination of computer applications and people,” he explained.
First, a genome machine “spits out” the millions of base pairs of an individual genome, said Lantos. Next, a computer program sifts through these pairs and boils them down to a subset. This “preliminary cut” might show a 100 genetic mutations that appear to be disease-causing, 19,000 that look harmless and 1,000 mutatations of unknown significance, he said.