As the UK Newborn Genomes Programme prepares for the recruitment phase of its NHS-embedded research study, David Budd, CEO of genedrive plc, comments on how whole genome sequencing in infants has the scope to kick-start mainstream use of genetic testing across the health system.
It’s a mere 69 years since Watson and Crick’s groundbreaking discovery of DNA, and less than 20 years since the Human Genome Project first laid out the genetic map of a person.
And yet, very soon we could have routine access to whole genome sequencing and analysis across our public health systems.
The UK Newborn Genomes Programme, in collaboration with the NHS, is exploring the benefits of incorporating whole genome sequencing into its routine newborn screening programme.
What was once deemed possible only in science fiction is now a reality that could eliminate suffering for thousands of babies and their families worldwide every day.
Improving the detection of childhood genetic disorders and variations
Nine babies are born each day in the UK with a genetic condition that could be prevented, treated, or even cured if a swift diagnosis were available.
On average, it takes five years for a child with a rare disease to receive an accurate diagnosis – a time punctuated by hospital appointments, tests, debilitating symptoms, and potential developmental delays or missed schooling, all of which could be better managed or reduced with earlier diagnosis.
Currently, five-day-old babies are invited to have the blood spot test – a minimally invasive procedure that involves a small prick on one heel and four spots of blood squeezed onto a testing card.
These samples are tested for biomarkers associated with nine genetic diseases including sickle cell disease, cystic fibrosis, congenital hypothyroidism, and six metabolic disorders.
We know that early recognition and intervention for these conditions can vastly improve the quality of life for babies, and even prevent symptoms from manifesting in the first place (as is the case for metabolic disorders when carefully planned diets are followed).
Excitingly, there is scope to expand this testing to cover genetic mutations implicated in a whole host of rare, potentially life-threatening, diseases.
More than nine in ten people carry a genetic variation that could alter their response to a drug.
Antibiotics are among the commonly prescribed treatments with existing pharmacogenetic implications that could be better managed with molecular testing in acute care.
For example, gentamicin is an antibiotic used empirically across the country to treat neonatal infections.
However, one in 500 babies is born with a predisposition to lifelong hearing loss on exposure to a single dose of gentamicin.
A new rapid point-of-care genetic test – MT-RNRI – identifies carriers of the MT-RNRI m.1555A>G mutation conferring susceptibility to hearing loss on gentamicin exposure, allowing clinicians to administer an alternative antibiotic even in emergency scenarios.
This simple test can save the hearing of up to 180 babies in the UK every year.
The ethical challenges
However, despite the irrefutable benefits of whole genome sequencing, routine use has a number of challenges.
Given that many genetic variants have an element of heredity, genetic testing often walks hand-in-hand with genetic counselling.
A gene variant found in one child may be present in other family members that have not themselves consented to genetic testing.
Also, additional subsequent children may also be carriers of variants, and so professional genetic counselling is paramount.
Actionable diseases are those that we can do something about, and are the only ones proposed for inclusion in routine newborn screening.
But even those which can be improved with treatment may never come to fruition if the mutated gene is not expressed.
Nervous families could spend years waiting for a disease that might never appear.
We also need to consider the cost of whole genome screening and how to implement it fairly.
It’s estimated that a newborn screening programme would cost up to £1bn per year if every child was screened.
Will it divert funding from other NHS applications? Will all ethnicities benefit equally?
Possibly not, if ethnic minorities remain underrepresented in the reference databases of genomic variation – used to interpret genetic differences.
Genetic testing for specific diseases produces a very discrete data set that generally cannot provide further prognostic or predictive information on an individual beyond the target gene being tested.
Where targeted testing can be thought of as understanding a specific word in a novel, whole genome sequencing reads and deciphers the entire novel, stores the data, and subjects it to current and of course future understanding of genetics.
Understandably, this raises the issues of data security and future misuse, and how to ensure that access is not extended to other agencies for unauthorised purposes.
Opening doors to future applications
Though there are many aspects of testing still to be ironed out, newborn whole genome screening is an exciting step towards routine integration of genetic testing into everyday medical care.
Sequencing for newborns represents a new frontier in screening and predictive medicine.
The routine use of genetics in UK healthcare will drive more awareness of DNA testing generally, including its growing use in acute and emergency medicine.
Strokes, antipsychotic drugs, and statins are all examples where urgent genetic testing has the opportunity to improve patient outcomes.
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