Whole genome sequencing for newborn screening

Whole genome sequencing for newborn screening
© iStock/tatyana_tomsickova

Sukhvinder Nijhar Nicklen, Market Development Leader at PerkinElmer, outlines the building blocks of an effective roll-out of Whole Genome Sequencing (WGS) in the UK.

The UK government’s Autumn Budget pledged £5bn towards health-related research and development, with a specific reference to genomic technologies including ‘Generation Genome’, a pilot programme to detect over 200 rare diseases in newborn babies. The government’s investment is a sign of the growing interest in genome sequencing in the UK. The Budget announcement did not happen without precedent – the last two decades have seen many milestone launches and technologies that have swayed public opinion on population screening.

One of the most notable recent launches was the introduction of Non-invasive prenatal testing (NIPT) to the existing NHS screening pathway in June 2021. Testament to the level of due diligence required to introduce new procedures on a national scale, the UK National Screening Committee (UK NSC) first recommended NIPT in 2016 and dedicated the following five years to conducting research and engaging the public to support a successful launch.

The UK NSC’s work shows significant screening changes do not happen overnight – and it is interesting to note the same long-lead techniques used by NIPT in 2016 are being applied to Whole Genome Sequencing (WGS) for newborn screening today. Here, we take a closer look at what whole genome sequencing is, the benefits it could bring for screening in the UK, and what the roadmap to its introduction looks like.

An overview of whole genome sequencing as a technology

One of the key objectives of genetic research in medicine is to link specific genetic identifiers with hereditary diseases. The sheer amount of information stored in human genomes – they contain between three to six billion DNA base pairs – means locating these links was once akin to finding a needle in a haystack. However, new laboratory techniques and sophisticated computer processing power boosted WGS out of the realms of theory, and the science was actualised in 2008 when Dutch researchers produced the first entire sequence of human DNA.

Following this proof of concept, the UK is one of many countries that has been looking to integrate WGS into its national screening programme. One of the big driving factors in the UK for a roll-out of whole genome sequencing is its ability to identify disease-causing genetic variants in what is known as the ‘non-coding regions’ of human genomes. While the coding portion of the genome (called ‘exome’) accounts for up to 85% of disease-causing variants, sequencing the whole genome, vastly increases the possibilities of finding dangerous mutations.

The UK roadmap to nationwide whole genome sequencing for newborn screening

The clinical benefits of whole genome sequencing for newborn screening speak for themselves from a research point of view, but a number of factors must be taken into consideration before whole genome sequencing is integrated into NHS care – and this is why significant changes with the rollout will not happen overnight.

It is undeniable that there will be a cost involved in the introduction of whole genome sequencing for newborn screening, as there would be for the implementation of any new medical procedure. These additional costs are justified by looking at long-term financial impact.

Imagine, for example, whole genome sequencing is used to identify a disease in a newborn that would not have been detected using traditional screening tests. If the disease was not identified and treated early, the patient may have needed multiple long-term hospital stays during which a barrage of expensive diagnostic tests are run. Alongside the obvious improvement on the patient’s quality of life, cases such as these represent a potential net financial saving over time by reducing the cost of long-term care incurred by hereditary disorders.

This aspect was also highlighted by The 100,000 Genomes Project study carried out in the UK. A preliminary report on a pilot study found that genome sequencing within the UK’s national healthcare structure delivered an increase in diagnostic yield across a range of rare diseases. While analysis of the study is still in its early stages, what we have seen so far is very encouraging.

The second important factor to consider is public opinion. This has been the focus of Genomics England, an initiative jointly funded by the National Institute for Health Research and NHS England to kickstart an ethical and transparent programme of genomic research in the UK.

In partnership with the UK NSC, Genomics England launched a major public dialogue in the summer of 2021 to not only help educate members of the public on the motivations behind the introduction of WGS, but to identify possible areas of concern where safeguards must be installed. This led to a set of recommendations for tackling issues that may not have otherwise been considered, such as the offering of counselling and mental health assistance for patients (or the parents of patients) who have received a diagnosis through WGS. This type of public engagement will be critical to the NHS in its exploration of WGS for newborn screening and will inform future rollout plans.

Maximising the clinical results

Other considerations that must be taken into account for the introduction of WGS relate to what happens in laboratory settings. The technology powering genetic testing is moving fast, so it is important to set and regularly review standards of clinical excellence in order to maximise clinical results.

These key standards include:

Turnaround time – the time elapsed between first testing a sample and seeing results will vary depending on the equipment used. These typically take up to two months, during which time critical treatment is not being administered to the patient. However, the latest equipment is capable of turning around genomes in 10-12 days.

Multiple sample types – especially in the case of newborn screening, sample gathering is not always a straightforward process. As the recent NHS blood vial shortage demonstrates, it is important that similar events would not impact the capabilities of newborn sequencing in the future. It is therefore preferable that testing equipment have the capability to test multiple sample types, such as saliva swabs, dried blood spots and genomic DNA.

Enhanced analytical techniques and expertise – Once a genome is fully sequenced, advanced analytical tools and the expertise of a clinical geneticist must be applied to understand both the patients genotypic and phenotypic data. The relationships between a patient’s genome and their clinical symptoms are complex and an expert understanding is required to unpick the biological relevance of the data.

Adhering to these and other standards for clinical excellence is of utmost importance to successfully continue on the roadmap to a wider introduction and take-up of WGS.

Sequencing: the future of genetic research

As the government tacitly acknowledged in its Autumn Budget, investing in medical technologies has the added clinical benefit of contributing toward the research and development of future innovations. MRI machines, for example, are not only useful for diagnosing illness – they can also help measure the effectiveness of new treatments and further our understanding of the human brain.

This is very much the case for whole genome sequencing. In addition to patient care, a sustained programme of whole genome sequencing – such as WGS for newborn screening – will produce an exceptional level of insights that will further genetic research, and help find new ways to understand, treat and even cure rare diseases.

It is a prospect which is highly exciting and well within reach but can only be achieved if both the public and private sectors take the right steps in the present. Right now, the government has signalled interest in developing and furthering genomic science, companies are working at breakneck speed on incredible sequencing technologies, and the future of whole genome sequencing feels bright.

Sukhvinder Nijhar Nicklen PhD
Market Development Leader

This article is from issue 20 of Health Europa Quarterly. Click here to get your free subscription today.


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