A recent study has demonstrated that through standardizing the whole genome sequencing process and making it routine for patients, we can improve rare disease diagnosis across the board. Earlier diagnosis often means better outcomes. Additionally, the routine implementation of this sequencing enhances research for future patients’ benefit.
This study was conducted thanks to collaboration by the NIH and Genomics England. It was published in Nature.
The Study
Whole genome sequencing is possible thanks to the 100,000 Genomes Project. This project was initiated to help make this genetic diagnostic testing routine. It has led to the discovery of the genetic causes of some diseases and has provided a diagnosis for hundreds of patients. Whole genome sequencing allows researchers to investigate almost all of a patient’s DNA. Current sequencing only investigates the genetic differences that are already thought to be likely to lead to disease.
A huge benefit of whole sequencing is that it allows for more than just genes to be studied. Scientists can look at what switches on genes and what causes them to dim in intensity. These can also cause disease, even though the gene itself isn’t at fault. These mechanisms specifically cannot be analyzed without investigating the full DNA sequence.
This study worked to integrate the sequencing as a routine procedure across the NIH. It led to an increased speed of diagnosis, from weeks to months. Additionally, it increased the likelihood that a patient would receive a diagnosis at all.
Patients with similar symptoms were studied in groups, depending on what area of the body was affected. The results were dramatic. For example, for patients who were facing early vision loss, 60% received a genetic diagnosis explaining why.
In total, 10,000 patients who were living with an undiagnosed rare condition had their genome sequenced. Not only were diagnoses provided, new rare diseases were uncovered. 172 million differences within the genomes of these patients were identified. Then, they worked to uncover which of these differences actually caused disease.
A total of 95 genes which are likely to be the cause of a patient’s rare disease were uncovered. 79 of these genes were found to cause disease within the patients in the study.
PI
In a subset of the study, 886 primary immunodeficiency (PI) patients had their genome sequenced. They were able to find 4 individual genes which were associated with PI. Understanding which specific gene is impacting an individual patient is essential for prescribing the best treatment and providing the best care for patients.
The Future
57 hospitals are currently in a network of centers focusing on rare disease, created by the NIHR BioResource. The goal is to ensure that scientific discoveries are not limited to the lab.
Additionally, the sequencing is now being used for COVID-19 patients to help understand why some patients present with more severe disease.
As a result of the evidence presented in studies like this, the UK announced back in 2018 that whole-genome sequencing would be provided for all those who were very ill and suspected of having a genetic condition. But, by 2024 it will be expanded to reach one million.
They are phasing in the process nationally as a new standard of care. As part of this effort, they are working to ensure that the implementation will be even across the country.
The benefits are endless. Faster diagnosis, reduction in costs, improved understandings, better treatment, and improved quality of life for patients are all a result of whole-genome sequencing and thankfully, its continuing to spread.
An average rare diagnosis in the UK takes approximately 2 years to come by. Hopefully, the standardization of this sequencing process will change that.
You can read more about this implementation here.
