By sequencing the complete genomes of 2,636 Icelanders, researchers from Amgen’s deCODE Genetics in Reykjavik hope to show how the technology can offer a whole new understanding of the roots of disease and human evolution. Using these data, large international teams have discovered a thousand genes that people can totally live without, revealed when the last common ancestor of all Y chromosomes lived, and identified variants in genes linked to liver disease and Alzheimer’s. The work, published as a series of four papers in Nature Genetics this week, is the largest set of genomes sequenced from a single human population ever.
“This work is a demonstration of the unique power sequencing gives us for learning more about the history of our species and for contributing to new means of diagnosing, treating and preventing disease,” Kari Stefansson of deCODE says in a new release. “It also shows how a small population such as ours, with the generous participation of the majority of its citizens, can advance science and medicine worldwide. In that sense this is very much more than a molecular national selfie.”
In this first study, researchers used the data to identify more than 20 million genetic variants that they say will help us understand the genetic basis of diseases, when combined with healthcare information and genealogical records. As a demonstration, they combined the data with other genetic information from another 104,220 Icelanders to see who among them carried these variants. They also found a variant of the ABCB4 gene that’s significantly linked with the risk of developing liver disease.
In a second study, researchers identified mutations in the ABCA7 gene that are associated with increased Alzheimer’s risk. And they found six of the eight mutations in ABCA7 in other populations of European ancestry, including people living in the U.S.
In a third study, researchers identified 8,041 people who are alive and well, but have lost the function of at least one gene. That means both copies of the gene (one from mom, the other from dad) aren’t working. In these individuals, the team found 1,171 so-called “knocked-out” genes. The most common type of knocked-out genes were olfactory receptor genes, which are responsible for our ability to distinguish different smells. Genes that are highly expressed in the brain, on the other hand, were rarely knocked out—suggesting that the loss of these genes are far more damaging.
And finally in a fourth study, by zooming in on 753 Icelandic men from 274 groups of related individuals, researchers were able to estimate the rate of mutations on the Y chromosome. Using this, they dated the most recent common ancestor of all human Y chromosomes to between 174,000 and 321,000 years ago. This estimate is pretty close to that of the most recent common ancestor for mitochondrial DNA, which is inherited from mothers.
“This is just sort of scratching the surface,” Stefansson tells Science.