Questions about sequencing healthy people, in particular children keep coming up constantly. Should we or shouldn’t we, what is the value of doing it? Let’s have a look what are the pros and cons in doing so. Why would we want to sequence healthy people?
Human genome consists of 20,000 to 25,000 genes and a large proportion of sequence previously known as “junk DNA”, which separates those genes from each other. As we are discovering the sequences between the genes are quite important and are not “junk” after all, but this is a separate topic. Our knowledge of what normal sequence is comes mostly from the known genes, which are only about 2% of the entire human genome. With an increase in whole genome sequencing (WGS) efforts we are now learning what makes the rest of the genome look “normal” and how does this non-coding sequence contribute to human health. It is important to remember that an average difference between two people is only 0.1% across their genomes, so it is not a lot, however, it makes us very different and very unique.
Sequencing only people with genetic disorders, cancer and a small proportion of healthy volunteers can lead to a bias in our knowledge of how a healthy or normal human genome should look like. Therefore, we need to sequence quite a lot of healthy individuals to determine what is a normal genome. I can hear you ask why looking at children, would not adult volunteers do just fine? Yes, and no.
Adult sequences are valuable, however, one of the questions they cannot answer is what changes occur in the 98% of the genome sequence as part of a human being growing up and developing. We know of some changes associated with epigenetic changes due to environmental or aging effects, however, our knowledge is relatively incomplete. Sequencing babies will allow us to follow them up and see if and how the whole genome changes over time. Any detected changes can then potentially be correlated to health of the individuals or their exposure to environmental factors.
An unintended result from WGS of a baby’s genome is identification of a rare early onset disease not usually tested for in newborn screening panels. Such findings can save a baby’s life by implementing preventative measures or early treatment. The argument here is, could this have been done without sequencing? And is this a cost effective measure for every baby born? The BabySeq project aimed to address some of these issues. There will be some serious decisions to make if we will continue with expansion of newborn panels as we know now or we will focus on creating sequencing panels to give babies a healthy start.
The main arguments of those who oppose rolling out genome sequencing for newborns and babies are:
- There is lack of evidence that it will be beneficial and cost effective if rolled out widely
- There needs to be a clear demonstrated benefit over potential harm which such sequencing can cause
- There are ethical issues of potential discrimination, finding risk for diseases which will not affect a person till the later decades of their life or finding sequence variants of unknown significance or how and if to return information about baby’s carrier status
How valid are those arguments will probably be debated over the next few years to make a final recommendation as to the testing of healthy babies. At the moment cost of whole genome sequencing is still too high to really roll it out as first line of testing, but as technology develops and costs are coming down a decision will have to be made probably sooner than we think.
The next question likely to arise is, if the whole genome sequencing (WGS) should be a direct-to-customer (DTC) service or should the ordering be handled by medical geneticist but make access easier for those who want to sequence their babies. Expansion of DTC genetic tests by a variety of companies is making this a very real issue and how likely are we to see companies not only offering a $99 soccer gene prediction test, genetic test for IQ, math skills etc but also offering WGS? Are those companies capable of delivering high quality sequence and high quality genetic reports?
As consumers we need to be sensible in why we want to test a baby and who does that testing. As the base of providers of WGS services increases, there will be more competition not just to the quality of sequence provided but also post-sequencing services and updates about new findings over time. Other critical parts of the service will be:
- clarity of the consent form and provision of genetic counseling pre- and post-testing
- security of the sequencing data
- clarity of the information provided back
- educational content of the website
- cost, as we have no idea who and how will be paying for WGS, cost could be a decisive factor
- value for money, consumers want to know what is included in the price and will there be any additional costs later or all is paid upfront
- ease of opting out of any research projects
In my opinion, there is value in sequencing newborn babies or infants as this can help them, their families and it can enhance our genetic knowledge. BabySeq project was a valuable initiative as it also taught us what interest is out there in WGS and how parents approach the process. Long term outcomes should help us make decisions over how the information can be used and what effects genome sequencing has on families not just a baby. It is also very important to realize that our approach to WGS may change and attitudes will reflect on how insurance companies are handling cases of individuals who have been sequenced and their families as well as on how sequencing is seen by the government policy makers.
References:
Abecasis GR et al (2012). An integrated map of genetic variation from 1,092 human genomes. Nature 491:56-65
Johnston J et al (2018). Sequencing Newborns: A Call for Nuanced Use of Genomic Technologies. Hastings Center Report, https://doi.org/10.1002/hast.874 (accessed 11/08/2018)
The BabySeq Project, https://www.genomes2people.org/research/babyseq/ (accessed 11/08/2018)
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