Two of the most frequent questions I am asked these days are: ‘Why is it so much easier to do genetic testing now?’ and ‘Why is it still so hard to do genetic testing now?’.
Both are very reasonable questions reflecting the realities of genetic medicine today.
Genetic testing is much simpler, faster and cheaper today than it was 5 years ago. The reason for this is that reading the genetic code – which is called DNA sequencing – is now performed in a completely different way. Previously, DNA sequencing was laborious and expensive as it required each letter of the code to be read one by one, sequentially. Now ‘next-generation sequencing’ is used and allows millions of short strands of DNA to be read all at the same time, in parallel. I describe this in the accompanying vlog.
Bottlenecks in genetic medicine
For 20 years, reading the genetic code was the bottleneck in genetic medicine because DNA sequencing was the most time-consuming and expensive part of the process. A significant activity in genetic medicine was directed towards prioritising and policing eligibility for genetic testing. For example, by using cancer family history to decide who should have a BRCA test, or heart and eye examinations to decide who should have a Marfan gene (FBN1) test.
The DNA sequencing bottleneck in genetic medicine has now been completely removed, because of the advent of next-generation sequencing. Instead, access to genetic testing and interpretation of genetic data have become the new bottlenecks.
Easing genetic medicine bottlenecks
An urgent priority for genetic medicine is to ease and remove the new bottlenecks. Fundamental changes in approach are required, including:
Radical review of genetic medicine requirements in an era of accessible DNA sequencing
We need to re-evaluate the suitability of genetic medicine processes now that DNA sequencing is fast and affordable. Many of the time-consuming, resource-intensive genetic testing eligibility processes are no longer necessary and no longer make sense. The cost and time of triaging access to testing has become much more than the cost and time of doing the test!. For example, it is scientifically, clinically and economically more appropriate to offer BRCA testing to all women with ovarian cancer, rather than only those that fulfil complex family history criteria.
Developing new genetic medicine processes instead of trying to ‘upscale’ old ones
We need to move away from trying to ‘upscale’ structures used in the era of small-scale testing in highly-selected individuals. Instead we need fundamental paradigm-shifting innovations in genetic medicine processes that match the paradigm-shifting advance in DNA sequencing.Variant interpretation exemplifies this need. Traditionally, evaluation of gene variants was performed on an individual variant basis. For each variant one would look at a gene-specific database and the scientific literature to decide it’s impact. This was an effective and appropriate process when only one or two genes were being tested in a few people. However, in the current era of multi-gene, exome or whole genome testing in many people, it is simply impractical for the hundreds of variants detected to be evaluated in this fashion. We need to integrate interpretation into the analytical pipeline such that automated interpretations can be provided for as many variants as possible and expert attention is directed to the small number of variants that require it.
What is the TGMI doing?
The TGMI is taking an holistic approach. We are addressing both the conceptual and practical requirements of genetic medicine today. For each of our four objectives, we are looking with fresh eyes to design processes that truly maximise the benefits of the extraordinary technological advances of recent years. In this way we hope to progress the enormous potential of modern DNA sequencing to improve global health.