When the first Viking explorers began settling Iceland, none could have imagined that their descendants would pioneer the future of modern medicine by surveying the human genome. Fast forward 1000 years to today, when an Icelandic company has revealed its success in sequencing the largest-ever set of human genomes from a single population. The new wealth of genetic data has already begun changing our understanding of human evolutionary history. It also sets the stage for a new era of preventive medicine based on individual genetic risks for diseases such as cancer and Alzheimer’s disease.
The milestone in genome sequencing comes from deCODE Genetics, a biopharmaceutical company in Reykjavík, Iceland. Their work, published as four papers in the 25 March 2015 issue of the journal Nature Genetics, has yielded new insights about the common human ancestor for the male Y chromosome—narrowed to somewhere between 174,000 and 321,000 years ago—based on their latest calculation of human mutation rates. Another part of their work discovered that about 7.7 percent of the modern-day population has rare “knockout” genes—genes that have been disabled by mutations. Early research has also revealed a mutation in the ABCA7 gene, which doubles the risk of Alzheimer’s disease in Iceland and other populations dominated by European ancestry.
“These are just a handful of observations that have come out of the ability to look at the sequence of the genome of an entire nation, ” said Kari Stefansson, founder of deCODE Genetics, during a press briefing on Monday, 23 March. “What is more, we are now sitting in Iceland with the possibility of taking advantage of these insights when it comes to the Icelandic healthcare system.”
The company sequenced the whole genomes of 2636 Icelanders and used those genomes as the basis for calculating the genetic variances for the entire Icelandic population. Iceland represents a unique laboratory for genetics researchers because much of the modern population traces its lineage to a relatively small number of founders; a fact that makes it easier to trace genealogies and pedigrees.
Myles Axton, chief editor of Nature Genetics, introduced the Monday press briefing by describing how the genetic sequencing strategy in Iceland could also work for other countries:
This strategy of sequencing the DNA of about 1 in 100 of the population, a total of 2,636 Icelanders, and then using shared sets of common genetic variance to predict the full spectrum of genetic variance carried by the whole population, is a great model for the future of human genetics. This technique can be applied to any population and is all the more accurate when there are pedigrees available for much of the population.
Genome sequencing has allowed deCODE Genetics to begin data-mining information about how certain genes function and their relationship to a broad array of diseases. Past findings from such research included additional insights about gene variants associated with Alzheimer’s disease and schizophrenia.
The growing database on knockout genes may prove particularly helpful when matched against the phenotypes of individuals—the physical traits or characteristics that can be observed. Perhaps unsurprisingly, the researchers found that knockouts are least common among genes expressed in the brain, given that organ’s importance.
“Basically what we hope to get out of phenotyping the carriers of these knockouts is to figure out which biochemical pathways are necessary for which physiological functions,” Stefansson explained. “Then the question is whether there is redundancy in some of these physiological functions; are there alternative biochemical pathways that can compensate for the loss of one?”
Such genetic information could prove lifesaving for Icelanders who carry mutations that make them vulnerable to certain diseases. That’s why Iceland’s government has already begun talking with deCODE Genetics about possibly using the genome-sequencing information within the country’s healthcare system. The effort could usher in a new era of preventive medicine based on information about each individual’s genetic inheritance, Stefansson said.
We could in Iceland at the push of a button find all women who carry mutations in the BRCA2 gene. The Icelandic mutation in the BRCA2 gene confers a lifetime risk of a lethal cancer for women that is 86 percent. 86 percent of carriers of the BRCA2 gene in Iceland develop a lethal cancer. The lifetime expectancy on average is 12 years shorter than the non carriers. They are 3 times more likely to die before the age of 70 than non carriers. This risk could basically be nullified by preventive mastectomies and ovariectomies.
The deCODE Genetics effort has also begun influencing the hunt for new pharmaceutical drugs. Stefansson’s Icelandic company was bought by the U.S. biotechnology firm Amgen in 2012. Amgen has used the genome-sequencing insights from deCODE Genetics team to cancel dead-end research projects and to start new drug discovery programs.
The Icelandic effort has also begun deliver what President Obama hopes to achieve in the United States with his announcement of the Precision Medicine Initiative during the 2015 State of the Union address, Stefansson said. But first, Icelanders are grappling with how to handle such sensitive genetic information without ignoring issues of individual consent and privacy.
A Nature Genetics editorial accompanying the four newly published papers touched on the ethics of how to use the deCODE Genetics information:
Because the deCODE genomic projects were consented for research, it would be ethically inappropriate for the researchers to contact the mutation-carrying individuals via their physicians. But, as enhanced cancer screening at younger ages than usually recommended for the general population can influence the health and life expectancy outcomes of mutation carriers and their relatives who also carry the mutation, to do nothing at all would also be ethically wrong. In our view, the decision lies with the Icelanders themselves once they have been given the information about the number of people at risk of these diseases and the options available.
For his part, Stefansson had no hesitation in recommending that Iceland’s healthcare system take advantage of his project’s big data approach to the human genome.
“I think it would be criminal not to take advantage of it, and I am fairly convinced that my fellow countrymen will begin to use it pretty soon,” Stefansson said. “It’s just one example, a tiny little example of what you can do when you have a deep insight into the genome of an entire population.”
Jeremy Hsu has been working as a science and technology journalist in New York City since 2008. He has written on subjects as diverse as supercomputing and wearable electronics for IEEE Spectrum. When he’s not trying to wrap his head around the latest quantum computing news for Spectrum, he also contributes to a variety of publications such as Scientific American, Discover, Popular Science, and others. He is a graduate of New York University’s Science, Health & Environmental Reporting Program.