An article published in the journal Nature reports that the 1000 Genomes Project (1000GP), which has reconstructed the genome of 2,504 individuals from 26 populations, describes a catalog of 84.7 million variants of the human genome. Despite great genetic diversity, most variants (86 percent of 84.7 million) are restricted to a single continental group, particularly among sub-Saharan populations in Africa.
The main objective of this international project is to catalog human genetic variation. Marc Via, professor in the Department of Psychiatry and Clinical Psychobiology and member of the Institute for Brain, Cognition and Behavior (IR3C) of the University of Barcelona, participates in the project. He has collaborated in sample design with the group Samples/ELSI (Ethical, Legal, and Social Implications). Andrés García Montero and Alberto Orfao, experts from the University of Salamanca, also participate in the study.
According to latest results obtained by the 1000 Genomes Project, every participant (healthy and over 18) contains 150 to 180 sites with protein truncating variants and 24 to 30 variants per genome implicated in rare disease. The project has contributed to characterize the history and demography of ancestral populations. For example, the project has proved a shared demographic history for all humans beyond 150 to 200 thousand years ago. Further, it has shown that European, Asian and American populations shared strong and sustained bottlenecks, all with less than 1,500 individuals, between 15 to 20 thousand years ago.
A large-scale map of human genetic variation
The 1000 Genomes Project is fostered by an international consortium composed by prestigious international institutions, 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).
Via explains that “the 1000 Genomes Projects is the first study dealing with genome variability characterization in worldwide populations. So far, studies were focused on individual genome sequencing but knowledge about population variability was lacking.” Its wide perspective turns the 1000 Genomes Project into a unique study, if we compare it with recent ambitious proposals.
By analyzing results, experts estimated that typical genome differs from the reference human genome at 4 to 5 million sites. Although most identified variants are rare (with a frequency lower than 0.5 percent), most variants identified in individuals’ genome are common (with a frequency higher than 5 percent).
Application of next-generation sequencing technologies
Development and availability of next-generation sequencing, technologies that enable study of every position of the genome and identify every genetic variant — from single nucleotide polymorphism (SNP) to chromosome duplications — is a key factor in the 1000 Genomes Project. “Next-generation sequencing has enabled to increase the number of analyzed genomes up to one thousand (the number that was intended and names the project),” explains Via. “Therefore, the project has sequenced every base of the complete genome of 2,504 participants on an average of seven or eight times, and their exome (the portions of the genes containing the information to synthesize the proteins and other molecules) on an average of 75 times. This resolution allows estimating that more than 99 percent of SNP that occur with a minimum frequency of one percent have been identified.”
Moreover, the project also includes the design of new statistical methods and computer algorithms to manage the great quantity of information that is generated in this type of study, establishing new standards for the scientific community.
“For instance, the project has been able to analyze the role that natural selection has played in recent processes of adaptation to local environments, and it has detected genes that are potentially under natural selection, although it has been observed that phenomena of strong natural selection are not frequent in human population recent evolution,” details Via.
Knowledge available to the international scientific community
The project, which has established the main characteristics of genome variation in populations from different continents, has provided international researchers with a reference framework for human gene variation, particularly shared and less frequent variants, which enables to improve the results of those studies that analyzes the relationship between genetic variants and rare diseases. “The project ends here. Genomic information, as well as the availability of biological material (cells or DNA), will be indefinitely available to the international scientific community,” concludes Professor Via.