Backers of the Genomic Sequencing and Newborn Screening Disorders research programme, unveiled today, say that it will test how useful and ethically sound it is for parents to know about their child’s comprehensive genetic makeup at birth and through childhood.
The programme will not replace the screening tests that most states require for newborns, which check for chemicals in the blood and defective proteins that signal the presence of nearly 60 genetic diseases. Instead, the grants will support research for studying whether sequencing a newborn’s DNA is better than conventional screening for detecting genetic disorders that affect drug metabolism, immune function and hearing, as well as some disorders that are included in conventional screening, such as metabolic disorders and cystic fibrosis.
“One can imagine a day when every newborn will have their genome sequenced at birth, and it would become a part of the electronic health record that could be used throughout the rest of the child’s life both to think about better prevention but also to be more alert to early clinical manifestations of a disease,” says Alan Guttmacher, director of the US National Institute of Child Health and Human Development, which is funding the new programme with the US National Human Genome Research Institute.
It now costs $1,000 or less to examine the protein-encoding portion of the genome and about $5,000 to sequence an entire human genome, so that day may be approaching quickly. And studies released over the past year have found that genetic sequencing might find a genetic cause for illness in 15–50% of children with undiagnosed diseases.
But geneticists and ethicists are divided over issues such as what information doctors should examine in a patient’s genome, how much of it should be reported to families and who should own and control this genomic data. Newborn-screening programmes have been controversial, with some states ordered to destroy blood spots collected through the programmes after activists argued that parents weren’t properly informed about the tests and their use in research.
“There’s great danger in sequencing newborns who have no say in the matter and whose parents may really have no clue what a Pandora’s Box they’re opening for themselves, their child, their future and their relationship,” says Twila Brase, president and co-founder of Citizens’ Council for Health Freedom in St Paul, Minnesota.
She points out that sequencing to screen for more conditions than are now examined will almost certainly uncover more false positives than current screening, and that screening results can have profound effects on families even if a child never becomes sick.
Officials behind the new programme say such ethical concerns are one catalyst for the newly funded research. “When you talk about a test that is done nearly universally among a section of the population, and done during the newborn period when one is completely incapable of offering individualized consent, it increases the importance of the ethical, legal and social considerations that are an intrinsic part of these grants,” Guttmacher says.
At the heart of these considerations is the question: what kind of genetic information about a child will doctors disclose to families? Just that pertaining to a child’s illness, or a broader range of results that could have implications for the child’s future health?
In March, the American College of Medical Genetics and Genomics (ACMG) recommended that doctors search the genomes of all patients receiving clinical sequencing for mutations in 57 genes linked health conditions and report these results back to patients, regardless of their initial reason for sequencing.
Geneticist Robert Green of Brigham and Women’s Hospital in Boston, Massachusetts, was on the panel that issued these recommendations and will be part of a team that plans to use programme funding to examine 480 genomes, half from healthy babies and half from sick babies in neonatal intensive care units. Green says that the team is still deciding what “appropriate risk variants to return” in the children from birth through early childhood.
Other grantees plan to follow the spirit of the ACMG recommendations. Cynthia Powell at the University of North Carolina at Chapel Hill will lead a team that will report genetic defects relevant to babies’ diagnoses. Her team will also tell parents about genetic mutations such as those on the ACMG’s list, which might not be relevant to their children’s diagnoses but could be “medically actionable”, such as a cancer condition that might emerge in childhood and could be preventable or treatable if caught early.
Powell’s group will also give parents the option to find out information about adult-onset conditions, and will develop a list of genetic results that should not be returned — primarily those linked to adult-onset, fatal and untreatable conditions, such as Alzheimer’s disease, she says. “In pediatric genetics, we are always concerned about predictive genetic testing in minors, taking away the right of a child not to know genetic information, especially for conditions that won’t manifest until adulthood,” Powell says.
But other geneticists, such as Stephen Kingsmore of Children’s Mercy Hospital and Clinics in Kansas City, Missouri, have been sceptical of the ACMG recommendations. “[H]aving to report the risk of future cancer syndromes for critically ill neonates or at end of life is absurd,” he wrote in a commentary in Science Translational Medicine in July, in which he estimated that screening the ACMG’s recommended genes in the general US population would yield 20 false positives for every true positive.
Kingsmore’s group has received a programme grant to sequence the genomes of 500 sick newborns and develop a sequencing test to diagnose the cause of their ailments within 24 hours. His team will first look for mutations in genes linked to the child’s symptoms. Then, if no results are found, his team will check the whole genome for disease-causing variants. His team may consider studying how families and doctors view results delivered according to the ACMG guidelines, he says.
But none of the teams receiving grants today are considering giving families their children’s raw genetic sequence data. That would allow families to seek their own interpretations of the data, or to keep it and have it reanalysed as the child grows up and researchers learn more about how genes influence health and disease.
Geneticist Robert Nussbaum of the University of California San Francisco, who is leading a team that will test whether sequencing is better than conventional screening at detecting some immune and drug-metabolism disorders, says that it is premature to consider releasing the raw data before it is proved useful through studies such as his own. “That would be jumping the gun a bit,” Nussbaum says.
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