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Adding value. NIH wants to know how genome sequencing could go beyond existing newborn screening tests.

U.S. Air Force photo/Staff Sgt Eric T. Sheler/Wikimedia Commons

NIH Studies Explore Promise of Sequencing Babies’ Genomes

In a few years, all new parents may go home from the hospital with not just a bundle of joy, but with something else—the complete sequence of their baby’s DNA. A new research program funded at $25 million over 5 years by the National Institutes of Health (NIH) will explore the promise—and ethical challenges—of sequencing every newborn’s genome.

The pilot projects build on decades-old state screening programs that take a drop of blood from nearly every newborn’s heel and test it for biochemical markers for several rare disorders. With some diseases, diagnosing a child at birth can help doctors prevent irreversible damage—phenylketonuria, a metabolic disorder that can be controlled with diet, is one example.

Newborn screening programs sometimes miss cases or turn up false positives, however. And they look for only a few dozen diseases, not all 7000 or so known or suspected diseases caused by defects in a single gene. “We can see the potential value of looking at an infant’s genome to examine all of the genes or perhaps a particularly informative subset of them at the beginning of life,” said Alan Guttmacher, director of the National Institute of Child Health and Human Development (NICHD), during a call with reporters today. Ever-cheaper sequencing is making this more feasible: An entire genome now costs $5000, and decoding just protein-coding DNA—the 1% of the genome known as the exome—can be done for $1000, compared with several hundred dollars to test for a single genetic mutation.

To explore how newborn genomes might be used in medical care, as well as the ethical, legal, and social issues this raises, NICHD and the National Human Genome Research Institute (NHGRI) are funding four projects. Two separate teams at the University of California, San Francisco (UCSF), and the University of North Carolina, Chapel Hill, will sequence the exomes of babies, some with known diseases, to see if genetic data can firm up the results of standard newborn screening. A third group at Children’s Mercy Hospital in Kansas City, Missouri, will study whether genome sequencing can speed the diagnosis of hundreds of genetic diseases in newborns sick enough to require neonatal intensive care.

The projects, which also include one in Boston, may also test for genes involved in metabolizing medicines in the hope that this can help prevent rare overdoses. But although they will decode an infant’s entire exome or whole genome, some teams will analyze the data only for genes on a narrow list. UCSF’s Robert Nussbaum says that it wouldn’t make sense to tell parents about, say, mutations in a gene called APOE that increases the risk of Alzheimer’s disease in adulthood. “For goodness sake, we don’t even have a clear idea about what to do about that in adults,” Nussbaum says.

Some projects may go further, however. The team at Brigham and Women’s Hospital in Boston and Boston Children’s Hospital will randomly assign 480 healthy and sick newborns to two groups—one that will receive conventional newborn screening, and the other that will also have their genomes sequenced. Over the next few years, the researchers will share results with parents and their doctors—including genes that raise the future risk of disease—then study how this information affects the child’s medical care. NIH wants to learn “how the parents feel and what they’re thinking, what results they would like, and also [work] with the physicians as to how much they understand and don’t understand,” said Tiina Urv, a program director in the NICHD’s Intellectual and Developmental Disabilities Branch.

Still, NIH won’t expect researchers to follow to the letter a recent report from the American College of Medical Genetics and Genomics on so-called “incidental findings,” which listed 57 disease risk mutations that the group felt should be reported to a patient when his or her genome is sequenced as part of routine clinical care. That list “was sort of a version 1.0” that “revealed a number of questions that need to be answered,” says NHGRI Director Eric Green.

In addition, because of the sensitive nature of newborn genomes, NIH won’t require researchers to submit the sequencing data to a shared research database, as the agency normally requires for adult disease studies.