Wellcome News 59 editorial

Five years ago, the International Human Genome Sequencing Consortium published its scientific description of the finished human genome sequence, the product of a 13-year effort to read the information encoded in our chromosomes. Science is most often an incremental endeavour, with research building upon previous discoveries, but the sequencing of the human genome is one of the rare examples where a field of study - in this case, human genetics - can be completely transformed by a single advance.

With the data freely available on the internet, researchers worldwide have a remarkable resource at their disposal. Comparisons with genomes of other organisms have brought fascinating insights into the extent to which our genes differ from those of the mouse, platypus, wallaby, chimpanzee and many other organisms from different branches of the evolutionary tree. Meanwhile, studies of people from around the world have provided glimpses at the spread of Homo sapiens out of Africa, as well as at more recent human history, such as the genetic legacies of Genghis Khan, the crusaders and colonial migrations.

Most importantly, rapid advances have also been made in studies of human biology: over the last few years, the human genome sequence has been used to help to uncover hundreds of genetic factors associated with human variation in health and disease. News stories on Trust-funded research from the last few months alone have reported on genetic links to traits that include infertility through premature ovarian failure, autism, synaesthesia, optimism and obesity. This issue of Wellcome News features the discovery of genetic mutations that can lead to progressive hearing loss in humans and mice.

Perhaps the most powerful applications of the use of human genome data have been genome-wide association studies, which take a systematic approach to the search for genes that influence our propensity to common diseases. In 2007, the Wellcome Trust Case Control Consortium - a collaboration that examined 14 000 people with one of seven common disease and 3000 controls - reported the identification of dozens of genetic variants linked to disorders including Crohn's disease, diabetes and high blood pressure. Subsequent studies have found many other variants linked to human disease; as reported in this issue, these include variants associated with an increased risk of heart disease and variants that confer protection against type 1 diabetes.

The Cancer Genome Project at the Wellcome Trust Sanger Institute is also taking a systematic approach to the identification of genetic mutations critical to the development of human cancers, mutations that can also be targets for new drug therapies. For example, the research team recently found mutations in the UTX gene in kidney cancer, melanoma and oesophageal cancer.

What has also become increasingly clear in the last few years is that the genetic control of our health is extremely complex, so there is still much to be discovered. For many common diseases, we know only a proportion of the genes involved, so the Trust has funded a series of further genome-wide association studies, most recently those investigating anorexia nervosa, pre-eclampsia, Wilms' tumour (a cancer of the kidney that affects children) and congenital heart disease. To help such studies, the Sanger Institute and centres in the USA and China are collaborating on the 1000 Genomes Project - the cataloguing of biomedically relevant DNA variations at a resolution unmatched by current resources.

Although genetic research often takes the headlines, studies into the environmental causes of disease are continuing in parallel. Projects such as UK Biobank that aim to bring these two areas together are therefore of crucial importance, as they will help us to understand how environmental and lifestyle factors interact with genetic factors and influence our health.

Mark Walport
Director of the Wellcome Trust