Friday, October 29, 2010

1,000 Genomes Project Paves Way For Greater Understanding Of Genetic Variation

The 1,000 Genomes Project, an international initiative that is probing genetic variation in humans, has released the results of its pilot phase. The initial findings already shed new light on the nature of genetic variation as well as its influence on disease, human history and evolution.

The study is published in the journal Nature, and the consortium's findings are available on the 1,000 Genomes Project website. The work was partly supported by the EU through the ADAMS ('Genomic variations underlying common behavior diseases and cognition trait in human populations') and READNA ('Revolutionary approaches and devices for nucleic acid analysis') project, both of which are funded under the Health Theme of the Seventh Framework Programme (FP7).

The overarching goal of the 1,000 Genomes Project is to catalogue human genetic variation by sequencing and comparing the genomes of 2,500 people from populations with origins in Europe, East Asia, South Asia, West Africa and the Americas. The aim of the pilot phase was to develop and compare different strategies for sequencing genomes on an unprecedented scale.

During the pilot phase, the researchers sequenced the entire genomes of 179 people and the protein-coding genes of a further 697 people. This effort generated an impressive 4.9 terabases of DNA sequence (i.e. 4.9 million million base letters). Processing this information required the development of a specialised computing platform and a number of software innovations. Analysing the data revealed millions of genetic variants, most of which were unfamiliar to the team.

'The amount of information delivered by this first stage of the project is remarkable,' commented Richard Durbin of the Sanger Institute in the UK. 'In less than 2 years, we identified 15 million single-letter changes, 1 million small deletions or insertions and 20,000 larger variants. The majority of these variants - around 8 million - had never been seen before.'

The results included some surprises. For example, it turns out that no-one carries a perfect set of genes; most people have between 250 and 300 genetic alterations that would prevent a gene from working normally and up to 100 genetic variations that have been associated with an inherited disease. However, as the researchers point out, everyone bears at least two copies of each gene, so as long as the second copy of the gene is in working order, individuals generally remain healthy.

The pilot phase included detailed investigations of a small number of family groups (mother, father and child). By comparing the genomes of the parents with that of the child, the team was able to work out how many mutations arise in each new generation. Their analyses revealed that each person has around 60 mutations that are not present in either parent.

Most importantly, the pilot phase demonstrated the effectiveness of the sequencing techniques used. 'We have shown for the first time that a new approach to sequencing - low coverage of many samples - works efficiently and well. This proof-of-principle is now being applied not only in the 1,000 Genomes Project, but in disease research, as well,' said Professor Gil McVean of the University of Oxford in the UK.

The project's findings are already contributing to genetic studies investigating traits as diverse as smoking and multiple sclerosis as well as cancer. 'By making data from the project freely available to the research community, it is already impacting research for both rare and common diseases,' explained David Altshuler of the Broad Institute of Harvard and Massachusetts Institute of Technology (MIT) in the US.

Looking to the future, the team has already embarked on the next phase of the project, which should be completed by 2012.

'The pilot studies of the 1000 Genomes Project laid a critical foundation for studying human genetic variation,' stated Dr Durbin. 'These proof-of-principle studies are enabling consortium scientists to create a comprehensive, publically available map of genetic variation that will ultimately collect sequence from 2,500 people from multiple populations worldwide and underpin future genetics research.'

For more information, please visit:
1,000 Genomes Project:
European Bioinformatics Institute (EBI):
Sanger Centre:
Citation:  The 1,000 Genomes Project Consortium (2010) A map of human genome variation from population-scale sequencing. Nature 467: 1061-1073. DOI: 10.1038/nature09534.

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