Human genetic variation mapped from 1,000 genomes

Over 1,000 people from 14 countries have had their genomes mapped by scientists. The researchers say their study will help them examine genetic variation at the scale of national populations and identify more are mutations associated with disease.

The international consortium, called The 1,000 Genomes Project, identified over 39 million mutations, most common and already known, but some rare. The rare variants were often restricted to specific local populations and many of these were described for the first time.

Professor Gil McVean of the University of Oxford, the lead author of the study said: 'Our research has found that each apparently healthy person carries hundreds of rare variants of genes that have a significant impact on how genes work, and a handful - from two to five - of rare changes that have been identified as contributing to disease in other people'.

The pilot study was launched in 2008 (reported in BioNews 442) and the first phase of the project involved the sequencing the genomes only six people. Since then the genomes of 1,092 people from the UK, Europe, East Asia, sub-Saharan Africa, and the Americas have been sequenced.

The scientists found that most common genetic variants are shared across global populations. However, according to Professor McVean, the most exciting find was that rare variants were usually geographically restricted. This information — and all the data is fully accessible to other researchers - will help scientists to interpret a person's genome in the context of the local genetic variation.

'The DNA donors in the study were not known to have any diseases, so this study gives us the genomic background we need for understanding which genetic variants are "within the normal range"', said Professor Aravinda Chakravarti of the John Hopkins School of Medicine in Baltimore, USA, who is involved in the project. 'With this tool, scientists now have a standard with which they can compare the genome of someone with diabetes, for example'.

However the study, published in the journal Nature, does have limitations. 'None of the 1,092 individuals in this project had their phenotype [their observable traits] characterised', Professor Eric Topol from the Scripps Research Institute, who was not involved in the study, told The Scientist. Without knowing the participant's phenotype, Professor Topol said, links cannot be made with the person's overall health.

Still, Dr Ewan Birney from the European Bioinformatics Institute, who is not part of the consortium, told The Scientist that 'The 1,000 Genomes Project is the backbone of our understanding for human variation. Both the data and the methods will be reused many times in the forthcoming decade'.

The final phase of the project, which is expected to finish next year, will sequence the genomes of a further 1,500 people from 12 new populations, including those in South Asia and parts of Africa.