Opening the book: How genome sequencing aids newborn screening
Ian Bolland caught up with Chris Hughes, managing director UK & Ireland of PerkinElmer, to discuss how its genome sequencing technology is used in newborn babies.
Many parents will be familiar with the heel prick test following a child’s birth and there is a good chance that PerkinElmer’s technology has been behind it. Newborn screening is currently based on biochemical testing on the instruction of a healthcare professional as a dry blood spot is analysed.
Chris Hughes, managing director, UK and Ireland, PerkinElmer described the biochemical testing and genome sequencing that is possible for newborns as “opening the book” on the child that is being screened.
The current system of screening in the UK involves biochemical tests run on newborn blood samples in the first few days of birth, looking for the following conditions:
• sickle cell disease (SCD)
• cystic fibrosis (CF)
• congenital hypothyroidism (CHT)
• phenylketonuria (PKU)
• medium-chain acyl-CoA dehydrogenase deficiency (MCADD)
• maple syrup urine disease (MSUD)
• isovaleric acidaemia (IVA)
• glutaric aciduria type 1 (GA1)
• homocystinuria (HCU).
The current criteria followed by the UK for screening conditions is based on the stipulations of the Wilson and Jungner criteria advocated by the World Health Organisation (WHO), amongst which include: the condition should be adequately understood; there should be facilities for diagnosis and treatment available; and clinical management of the condition should be optimised in all healthcare providers.
The number of conditions screened for varies per country (and follow different criteria) but PerkinElmer’s newborn screening solutions can identify more than 50 congenital disorders. Whole genome sequencing, on the other hand, offers an additional layer of screening to test for a wide range of genetic markers for several rare and otherwise difficult to detect disorders.
Explaining PerkinElmer’s process, Hughes said: “Blood spots are very robust, it’s something that PerkinElmer is very good at; we are the people who are best placed to sequence from dry blood spots because it isn’t as easy as it sounds. Most people will be going for saliva or DNA extracted from blood.
“The first step is to extract the DNA from the sample, so we’ve got an instrument called chemagens. Essentially, a sample comes into an instrument, uses magnetic beads to suck the DNA onto these magnetic beads and bind them together.”
From there, Hughes explains, magnetic rods take the beads out of the sample and within the same instrument it is washed several times just to increase the quality of the sample you’ve got. After extracting the DNA out of the sample, it needs to be prepared for sequencing.
Hughes continues: “We have a suite of reagents which will chop the DNA up into the fragments you need for sequencing and the liquid handling.
“Once the sample is prepared, we’ve got instruments which are checking for the amount of DNA, something that we call Victor NIVO, and then the quality of the DNA you’ve got. Sequencing is the most expensive part of the process, so you want to make sure that you’ve got enough DNA and what you do have is of high quality.”
“From there we are going into the sequencer, which is owned by sequencing company Illumina, and PerkinElmer operates its pieces of equipment, essentially at the end of the lab process. The data has tellers using artificial intelligence and machine learning to interpret the data, but this is done under the supervision of the human eye so anything that comes about matches with the clinical presentation.”
With individuals becoming more accustomed to testing at home throughout the pandemic, Hughes feels that this genome sequencing technology feeds into the idea of the strategy towards public health coming from a more preventative angle to battling certain diseases and conditions, rather than reactive – and cites the example seen in professional football in recent years.
“You’ve got a population now that’s used to the idea of diagnostic testing because I don’t know how many COVID tests that you’ve had but many will have multiple for their children as well. The whole point of whole genome sequencing is you get all the information, so you can be screened for diseases not that we’d just be looking for at thepoint of birth.”
“You’re probably familiar with Fabrice Muamba, and other people who have collapsed on football pitches, that’s a genetically inherited heart condition. Essentially if we screen the population for that we’d have less incidents where seemingly healthy people can have real problems out of the blue.”