The past few years have seen a huge increase in the identification of rare and common genetic variants associated with disease, advances made possible through ever cheaper and faster genome sequencing technologies. In the UK, the goal of the new NHS Genomic Medicine Service is to harness this knowledge in order to provide personalised treatments and interventions for patients. However, several challenges must be overcome in order to make this bold vision a reality. One is the need for many more genome sequences, in order to capture the full range of human genetic diversity and accurately interpret its implications for health.
Building on the findings of the recently completed 100,000 Genomes Project, plans are afoot to sequence the genomes of several million people within the next five years. Many of these will be NHS patients, with whole genome sequencing to be offered to seriously ill children and adults with certain rare diseases or particular cancers. Some genomes will belong to participants in UK BioBank, which is studying the health and wellbeing of 500,000 volunteers recruited between 2006 and 2010. The source of the remaining genomes is less clear – a plan to sell genome sequencing to healthy people was met with alarm earlier this year, with concerns that such a scheme risks creating a 'two-tier' service that goes against the core NHS principle of free healthcare at the point of delivery.
Meanwhile, the burgeoning direct-to-consumer (DTC) genetic testing industry offers people a wide range of tests that claim to provide insights into traits including ancestry, sporting ability and disease risk. Some companies now offer 'whole genome sequencing' – but what are the potential benefits and current limitations of such services? I recently had the opportunity to find out, as a participant in a project entitled 'Love My Genome', in which myself and others with a personal or professional interest in genetics were offered genome sequencing in exchange for sharing our experiences.
My reasons for wanting to take part were both personal and professional. The rate of progress in human genetics since I carried out my PhD project in the early 1990s, the 'pre-genome' era, is nothing short of astounding. Work that once took years may now be completed in a matter of weeks. So my initial reason for jumping at the chance to investigate my own genome was pure curiosity. From a personal view, I was keen to find out if there were any genetic clues that might shed light on common health conditions affecting myself and my family. With their agreement, I duly filled out consent forms and sent off a saliva DNA sample.
Some weeks later, a trained genetic counsellor took me through the main findings in my 150-page report. Having embarked on the project with excitement, I found myself unexpectedly nervous as the online session began. Thankfully, like most healthy people, my genome is reassuringly boring with no results flagged up in the red 'very important' sections. So based on a relatively short list of known harmful genetic variants – such as gene mutations associated with familial cancers – there were no clinically actionable findings in my report. Even though I'm fully aware that new disease variants are discovered on almost a daily basis, it was a relief to hear that my long-term health is less likely to be threatened by a genetic predisposition to a serious illness.
The analysis also looked at thousands of other variants, including those associated with slightly increased or decreased risk of a range of common health conditions such as heart disease and those that affect the body's ability to metabolise drugs, as well as determining my carrier status for many recessive genetic conditions. There was also a section in the report on variants associated with non-disease traits such as muscle endurance (increased) and snacking behaviour (typical), and some ancestry information. In addition, my genome revealed I am very likely to have blue eyes and blonde hair, a fact which – although not surprising to me – does demonstrate the increasing potential power of genomic analysis in forensic profiling.
As our genomes were sequenced by a commercial service, rather than a research centre, the report we received is based on a highly curated list of genetic variants with a proven involvement in a particular disease or trait. Although it was a very comprehensive genetic test, it just looked at a few percent of the 6 billion base-pairs that make up a human genome. In addition, it focused solely on SNPs (single nucleotide polymorphisms), 'single letter' changes in the code. Larger and more complex genetic changes such as structural variants (deletions, duplications and inversions) or repeats are not currently included in this type of analysis, as they are more technically challenging to identify and interpret.
Despite initially feeling rather disappointed at not being sent my entire DNA sequence to trawl through, I fully appreciate the reasons for reporting only those findings that are backed up with published, peer-reviewed evidence. This knowledge base is continually increasing, so our genome reports can potentially be updated, but there are still many 'variants of unknown significance' currently in the databases. Which leads me to wonder, how practical will it be for individuals like myself to donate their genome sequence and health information to help address this issue, should they wish to do so? These and other knotty problems remain to be resolved, as we head into the new era of genomic medicine.