Despite protests and some mutterings that it’s unethical, a British programme, similar to one launched in New York last year, will begin genome sequencing on 100 000 babies this year to analyse whether screening them for a wide range of conditions is beneficial.
The Newborn Genome Programme is led by the British Government-run Genomics England, which later this year will begin sequencing the genomes of up to 200 000 newborns in England over a two-year span.
The $126m project, being run by the National Health Service (NHS), will allow parents to opt into the tests, which would screen for around 200 genetic diseases, more than what traditional tests already screen for, reports Forbes.
The aim is to help treat diseases that require early detection for best chances of a healthy life, according to the study’s website, and ultimately will help the government decide whether screening babies for a wide range of diseases is beneficial.
America has a similar project that launched in September 2022 called the Guardian Study, a four-year research programme that will test 100 000 newborns in New York City for around 160 treatable disorders.
Background
The UK uses a standardised heel prick blood test for infants at five-days-old, screening for nine rare health conditions, like sickle cell, cystic fibrosis, inherited metabolic diseases and congenital hyperthyroidism.
In the US, all states require newborns to undergo screenings for several dozen genetic, metabolic and developmental disorders, including phenylketonuria, sickle cell, critical congenital heart disease and hearing loss: tested disorders vary by state.
Genomic sequencing offers an expanded, more advanced screening than the heel prick tests, but is not without controversy.
Critics
The Hastings Report, a peer-reviewed journal that explored ethical questions in medicine, noted in 2018 that since many genetic diseases are untreatable, and the health consequences of a lot of mutations are unknown, caution ought to be exercised before widely implementing genomic screening, saying evidence to date “does not support genome-wide sequencing of all babies at birth”.
Concerns have risen in part because although a patient may have a certain gene or gene mutation, this doesn’t guarantee they will develop the disease, according to the US Library of Medicine.
Because genome sequencing can test for thousands of conditions, some people worry having access to all potential health risks (even if they don’t occur) would be detrimental, according to feedback from a findings report by Genomics England.
Frances Flinter, a professor of clinical genetics and a bioethicist who works for the NHS, is concerned this type of research may be a “step into the unknown”.
“We must not race to use this technology before both the science and ethics are ready,” she said to Science Media Centre. “This research programme could provide new and important evidence on both. We just hope the question of whether we should be doing this at all is still open.”
When does genome testing happen?
Whole genome sequencing is usually used when a gene panel or single gene test doesn’t give a clear diagnosis. According to Yale Medicine, whole genome sequencing can help doctors identify learning delays and intellectual disabilities, and closely analyse a patient’s genes for health indicators or mutations.
Genome sequencing can diagnose most of the more than 6 000 disorders listed in the Online Mendelian Inheritance in Man database (a decades old catalogue of Mendelian principles created by biologist Gregor Mendel on traits and disorders).
Because most of the diseases tested are either rare (fewer than 2 000 reported cases in live births) or ultra rare (fewer than 100 people diagnosed within medical history), they would’ve gone undiagnosed without prior examination, according to a study published in the Canadian Medical Association Journal.
Surprising fact
A five-week-old infant was taken to a San Diego hospital in October because he wouldn’t stop crying. After a CT scan found brain abnormalities, a team did genetic sequencing on him and found a mutation for a severe vitamin B metabolic disorder. The infant’s formula was spiked with needed vitamins and his condition subsided, according to the New England Journal of Medicine.
Researchers believe this might have been the same condition that led to his infant sister’s death 10 years prior when genetic testing wasn’t as advanced.
Privacy concerns
Because policies around genome sequencing are vastly unregulated, according to the American Association for the Advancement of Science’s journal Science and Diplomacy, privacy concerns have grown. Genetic data can not only give a look into who the patient is, but it can also give insight into their relatives.
Law enforcement has been known to use genealogy websites to identify crime suspects.
Although the NIH keeps genomic data stored as unidentifiable, according to Standard Medicine, when combined with other public data sources, genomic data can be re-identified: Researchers can cross reference separate material with the genomic data and figure out which individual the anonymous data belongs to.
Big number
An eye-watering $100m: that’s what genetic sequencing cost in 2003. The price has drastically fallen, to a little under $10 000 in 2013 and then to less than $1 000 today, said the National Institute of Health’s National Human Genome Research Institute.
How genome testing works
All organisms have a unique genome (or genetic code) made up of nucleotide bases (labelled as either A, C, T or G). When the order of these bases is discovered via sequencing, the organism’s unique DNA pattern is determined.
There are four types of molecular genome tests. Targeted single variant tests look for a specific variant in one gene, single gene tests look for any genetic changes in one gene, gene panel tests look for more than one genetic change in one gene and whole genome sequencing analyses most of a patient’s DNA to find all genetic variations.
The UK study uses whole genome sequencing, and according to the Centres for Disease Control and Prevention, the process follows these steps:
1. DNA shearing: Scientists cut DNA using molecular scissors into tiny pieces small enough for a sequencing machine to read.
2. DNA barcoding: Similar to how barcodes at grocery stores identify a product, pieces of DNA barcodes (small pieces of DNA tags) are added to figure out which pieces of the cut DNA belong to which bacteria.
3. DNA sequencing: Scientists then combine the barcoded DNA from multiple bacteria and put them in a DNA sequencer. The sequencer machine identifies the A, C, T and G bases that make up each bacterial sequence. Then, the sequencer uses the barcodes to keep track of which bacteria belongs to which base.
4. Data analysis: Finally, scientists use a computer analysis tool to compare sequences from the different bacteria and find any differences among them. The number of differences tells the scientists how likely it is that the bacteria are from the same outbreak and how closely related they are.
Canadian Medical Associated Journal article – Genome sequencing as a diagnostic test (Open access)
See more from MedicalBrief archives:
Natural selection weeding out unfavourable genomes in Alzheimer’s
Study queries usefulness of genome sequencing in primary care
Scientists construct human gene ‘atlas’