A major project to sequence the genomes of 1,092 people from a range of different ethnicities has generated a detailed map of millions of genetic variations ranging from both rare and relatively common single nucleotide polymorphisms, to major chromosomal abnormalities. The results, published in Nature by the 1,000 Genomes Consortium, are being made freely available for scientists to exploit in disease-related research, and studies on the spread of genes and the genetic evolution of populations around the world. Importantly, researchers will also have access to cell lines from all 1,092 individuals.
The final map from Phase I of the project, generated from the genomes of people from 14 populations in Europe, East Asia, sub-Saharan Africa, and the Americas, includes some 38 million SNPs, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. The investigators say the map includes about 98% of all those SNPs present in less than 1% of a population.
Interestingly, the results found that rare gene variants tend to be constrained within particular geographic regions, as they are more likely to arise from more recent mutations. And it's these rare genetic variants, found in less than 1% of a particular population, that are thought to contribute most to the development of some diseases. “The implication is that the interpretation of rare variants in individuals with a particular disease should be within the context of the local (either geographic or ancestry-based) genetic background,” the researchers write in their published paper, titled “An integrated map of genetic variation from 1,092 human genomes.”
Notably, the results indicate that we all carry potentially hundreds of variants that impact directly on gene function, and a number of those that we already know can contribute to disease. “We are all walking natural experiments,” remarks lead author Professor Gil McVean, Ph.D., at Oxford University, U.K. “Some of our genes are switched off, some are active, while others are overactive. 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.”