Experts say that genetic sequencing may be the future of medicine, shaping how we understand and ultimately treat disease. If that’s the case, then the people of Iceland have a leg up on the rest of us.
In four groundbreaking papers published in Nature Genetics, scientists from Iceland describe the results of a massive gene-sequencing effort involving 2,636 people. Because the island country is relatively isolated, it’s a genetic goldmine. It enjoys a founder effect, which means that most residents can trace their lineage back to a few founding fathers, and that genetic variants have been passed down from generation to generation. That makes it possible to infer the distribution of the genetic variants found in the study’s 2,636 people to the remaining 325,000 Icelanders.
When they did that, the researchers, led by Kari Stefansson, CEO of deCODE Genetics/Amgen, were able find mutations linked to Alzheimer’s disease, liver disease, thyroid disorders and atrial fibrillation. They also identified almost 8% of the population who have lost function of at least one of their genes and calculated the rate of mutations in the Y-chromosome among men.
In recent years, the practice of mining large numbers of human genomes by comparing people with and without specific diseases has led to a growing list of genetic culprits behind conditions such as Alzheimer’s, cancer and more. But by studying such a genetically unique population, Stefansson says, he was able to pick up even rare genetic changes that have emerged more recently and occur less frequently but might still be important contributors to disease. Those, he says, will be important clues to better understanding the biological roots of health problems, as well as finding new drugs and treatments for them. “What we anticipate is that all human diversity is going to be explained by the diversity in the sequence of the genome, either solely by the diversity in the sequence or by the interface of that diversity and the environment,” he says. “That includes the diversity and risk of disease and the ability to resist them.”
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The mutation associated with Alzheimer’s, for example, in the ABCA7 gene, hasn’t popped up in previous searches, but the gene is involved in transporting lipids across membranes, a process that may contribute to the build up of sticky protein plaques in the brains of Alzheimer’s patients.
The people who have lost function of at least one gene—called knockout genes in the genetic world—could also provide valuable hints about the pathways to disease. Even with a gene knocked out, most of these people are functioning, and Stefansson says researchers still study them in more detail to figure out how they are affected by their non-functioning genes. In animal research, knockouts are useful to see how prominent and important a gene is for health functioning. Stefansson anticipates that there may be redundancies built into the human genome to compensate for some knockouts, so finding these backup systems might be key to understanding why certain people get sicker with a disease while others remain relatively unaffected.
The sequences are also giving scientists a sharper picture of our past. The Y chromosome analysis shows that the last common ancestor sharing the Y chromosome among homo sapien men dates back 239,000 years, putting it closer to the common ancestor for the mitochondrial DNA passed down by women via their eggs. It also revealed how quickly mutations on the Y chromosome are occurring, which “gives us information about the age of our species, which is related to how diverse we are,” says co-author Agnar Helgason of deCODE and University of Iceland. “It tells us how quickly we are evolving.”
deCODE, which was acquired by the biotechnology company Amgen in 2012, is also investigating the new trove of genetic information for possible drug targets. “What this kind of work and insight into the human genome does is make approaches to influence the genome [and find treatments for disease] more rational,” says Stefansson.
How quickly that will happen isn’t clear yet, but having more information could make the process more efficient. “I’m willing to go so far as to say that there is nothing in human nature that may not have a reflection in the genome, or have something in the genome that associates with it,” he says. “We are made from the basis of the information coded in the genome.”