1. ESRC Genomics Network (archive)
  2. Gengage
  3. The Human Genre Project

Egenis · News

A question of interpretation



An NHS hospital is decoding the genes of individual patients. Dr Susan Kelly discusses the issues.


Whole exome and genome sequencing is now feasible and entering clinical practice (writes Dr Kelly), as evidenced by the recent announcement by clinicians at London's Royal Brompton Hospital of a project to provide whole genome sequences to 10,000 cardiac patients to search for genetic risk factors to heart disease.

The project has been heralded as a further step in the direction of ‘personalised medicine’ in which prognostic, diagnostic and treatment decisions are driven by knowledge of an individual patient’s genetic risk factors as identified through such sequencing. As sequencing technologies become faster and cheaper, there appears to be much impetus to ‘sequence’ all patients, perhaps even as newborns. While this sounds exciting, whether and how such information will prove clinically useful requires a great deal of thought.

It is important to recognise that analyzing a person’s genome is a separate activity from interpreting it, and interpretation is the point from which clinical utility will be derived. The clip of genetic counselling that accompanied some news reports of the Royal Brompton's cardiac sequencing project was disheartening, as the counsellor appeared to interpret an individual’s risk of disease solely on the basis of sequence data. Unfortunately, much of what is being identified as ‘genetic risk’ for common complex diseases is in the form of many genetic variants that individually make up only a small contribution to overall risk, with a great deal of ‘risk’ being unknown, or environmental. Individual risk counselling on the basis of whole genome sequencing will be time-consuming and difficult, and involve significant knowledge of an individual’s family history, life history, and behaviours. It is also likely to involve counselling patients about risks for diseases for which they did not know they were being tested - Alzheimer's disease for instance – as the whole sequenced genome is likely to identify a range of risk variants we all carry in some form. Unless handled carefully and proactively, this may amount to predictive testing without prior consent.

These are but a few issues raised by the movement of whole exome and genome sequencing into clinical settings. It is critically important that the ‘dots’ between rapidly developing technologies and the much heralded vision of ‘personalised medicine’ be connected, and I would urge this as a health system priority.