NEW YORK (GenomeWeb News) – In a new study appearing online today in Nature, members of the 1000 Genomes Consortium reported that they have started cataloguing structural variation in the human genome at the population level.
By sifting through genome data for nearly 200 individuals, the team turned up tens of thousands of structural variants in the human genome, including nearly 2,000 changes affecting full genes or exons. The findings are helping to pinpoint parts of the genome that are particularly prone to such variation. In addition, those involved in the effort argue that a more complete understanding of these structural variants and their consequences could provide a peek into some previously unappreciated sources of disease risk.
"Knowing the exact genetic sequence of SVs and their context in the genome could help find the genetic causes for as-yet unexplained diseases," corresponding author Jan Korbel, a genome biology researcher at the European Molecular Biology Laboratory, said in a statement. "[T]his may help us understand why some people remain healthy until old age whereas others develop diseases early in their lives."
Members of the 1000 Genomes Project are working to characterize genetic variation in some 2,500 human genomes representing populations around the world. The team reported on initial findings from the pilot phase of the study last fall.
For the current study, members of the 1000 Genome Project's Structural Variation Analysis Group used breakpoint and other analyses to find structural variants, particularly deletions, in 185 human genomes.
The genomes, which were sequenced using Illumina, Roche 454, and SOLiD platforms for the 1000 Genomes pilot phase, represent 179 unrelated individuals and six individuals from parent-offspring trios.
In the process, the researchers uncovered 28,025 structural variants, including 22,025 deletions and 6,000 insertions and tandem duplications.
In particular, the researchers noted, there seem to be around 51 "hotspots" in the genome where structural variants crop up more often than usual. Among them are several regions previously linked to a genetic syndrome affecting congenital brain development.
Because copy number changes have been implicated in a host of other human diseases, ranging from cancer and Crohn's disease to autism and schizophrenia, researchers are keen to continue exploring these structural changes in the context of disease risk and progression.
With the new population-level catalog of CNVs in hand, the researchers explained, it should be possible to do more in-depth genotyping and CNV imputation studies involving even larger groups of individuals.
"Identifying [structural variants] from DNA sequencing datasets is very challenging and it is gratifying to see the incredible progress that the [Structural Variation] group has made over the past [two] years," 1000 Genomes Project Co-chair Richard Durbin, a researcher at the Wellcome Trust Sanger Institute, said in a statement. "I am confident that this map will serve as an important resource for future sequencing-based disease association studies."
Data from the new study is being made available to other researchers through the 1000 Genomes Project website.