1000 Genomes Project

By Marc Via, University of Barcelona

According to findings published in Nature, the international consortium 1000 Genomes, promoted by research groups from the United States, Germany, United Kingdom and China, has sequenced the genome of 1,092 people intending to shed light on the genetic contribution to disease.

Although more than 99 % of human DNA sequences are the same, the remaining 1 % can explain the individual differences. The central purpose of the 1000 Genomes Project is to catalogue human genetic variants. In this scientific challenge some prestigious international institutions participate, such as the Wellcome Trust Centre for Human Genetics (United Kingdom), the University of Oxford (United Kingdom), Harvard University (United States), the Broad Institute of MIT and Harvard (United States), the University of Washington (United States) or the Max Planck Institute for Molecular Genetics (Germany).

Studying human genetic variation

According to one of the main authors of the study, the professor Gil McVean at Oxford University: “Our research has found that apparently healthy individuals carry hundreds of rare variants of genes that have a subtle impact on how genes work and a handful (from two to five) rare changes that have been identified as causing a disease in other people”.

Marc Via from the University of Barcelona, expert on studies about genetic epidemiology and human population genetics and one of the authors of the article, states: “The 1000 Genomes Project has allowed us to identify different variations of human genome in a more accurate way than in previous studies, focusing on its application to biomedical genetics”. “One of the things that makes this project different is the wide range of populations represented”, explains Marc Via, collaborator on the sample design of the research made by the group Samples/ELSI (Ethical, Legal and Social Implications).

According to Via, “A remarkable effort has been made in order to get a representative population sample from all the continents and to make it useful for the current studies in human population biomedical research. For example, in Europe, 5 populations were registered which represent the opposites sides of the variation within the continent, and the same has been made in the case of America, Asia, etc. This helped us to get a higher percentage of genetic variation at different levels (inside and outside the continents) which represent variation patterns occurred at different moments all over the planet”.

Thousands of deleterious mutations in the human genome

This international study describes a catalogue of 38 million mutations in a single nucleotide of the DNA, named ‘single nucleotide polymorphisms’ (SNPs), present in human population. In addition, 1.4 million short insertion and deletion variants, and other sources of human genome have been identified. “More than a half of the 38 million SNPs identified are new polymorphisms unknown until now, and a great number of them are mutations, low frequency ones, which deprive the biological function of any protein or gene. Actually, all of us carry potentially deleterious mutations in our genome”, says Marc Via, who made his postdoctoral studies at the Institute for Human Genetics (University of California, San Francisco) directed by Esteban G. Burchard, co-author of this study.

The 1000 Genomes Project, which includes families (mother, father and children) in the population sample, has also been essential in performing comparative genome studies between parents and children. This protocol allowed to identify the number of mutations which appear in each new generation and to know the genetic recombination rate at a level of resolution never known before. But the advances do not finish here: scientists have also been able to attain another scientific challenge: to reconstruct in an optimal way the parents’ chromosomal phase through the child haplotype characterization.

Future goal: sequencing the DNA of 2,500 people The 1000 Genome Project is an important data collection of human genetic variation. Furthermore, it multiplies the ability to detect gene variants that can be related to diseases and it helps to set new links between molecular genetics and biomedicine. In future phases, the project will create an accurate map of genetic variations of the DNA sequences of about 2,500 people from all over the world.

This international researching effort aims at becoming an informative corpus about human genome which promotes research about the genetic origin of some diseases (multiple sclerosis, heart diseases, cancer, etc.) and helps to define more precisely the known and unknown genetic risk factors through the Genome-Wide Association Studies (GWAS) which are already getting some findings.

As Marc Via concludes, “The 1000 Genome Project is not only a scientific project that answers some of the questions posed, but it also is a really useful tool at any worldwide researcher’s disposal. One of the greatest challenges we have in front of us is to analyze this enormous amount of information and translate it into the clinical side”.

University of Barcelona
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