DNA sequencing had a transformational impact on biomedical science and paved the way for the Human Genome Project. The introduction of massively parallel, high-throughput ‘next-generation’ sequencing technologies early in the 21st century was an important breakthrough, but it soon became apparent that innovation would quickly eclipse even this approach and make rapid, affordable whole genome sequencing a reality.
Recognising the potential of genome sequencing as a transformative tool, the PHG Foundation undertook the world’s first comprehensive overview of the impending medical impact of human genome sequencing. Working with expert stakeholders from many different fields, we evaluated the different sequencing techniques in use and development and considered the potential clinical applications. Whole genome sequencing offers the opportunity for clinical genetics services to massively expand their ability to diagnose and characterise rare and serious heritable genetic disorders.
We found that, besides enlarging the scope of clinical genetics and underpinning the development of potential new therapies for genetic diseases, whole genome sequencing also presents a major opportunity for other areas of medical and public health practice. Cancer diagnosis, prognosis and treatment monitoring were poised for revolutionary advances, and the increasing availability of genetic tests had implications for all sorts of other specialties, for accurate diagnosis and better management of patients with underlying genetic disorders, as well as identification of at-risk family members. In public health, using whole genome sequencing to characterise and track infectious disease agents was an exciting prospect.
The projected impact of genome sequencing on the UK National Health Service was significant; we recommended immediate implementation wherever genomics offered clinical or financial benefits over existing tests. To achieve this, we identified key issues that warranted attention, including health professional education and guidance, commissioning pathways and criteria, and service provision. Similarly, the wider implications of clinical genome sequencing called for urgent action – notably for the NHS to develop a standardised database of normal and disease-linked genetic variations and infrastructure and expertise in bioinformatics (analysis and interpretation of DNA sequences). Consideration of the relationship between health service providers and patients and their rights and responsibilities would be essential.
The 2011 report, Next Steps in the Sequence, was presented to the UK government advisory body, the Human Genomics Strategy Group, who drew on its content and recommendations in designing health service strategy. This in turn led to the establishment of the 100,000 Genomes Project run by the new NHS-owned company Genomics England. The PHG Foundation continues to advocate, inform and support the introduction and expansion of whole genome sequencing and related applications in clinical and public health services.