Iceland paint a genomic picture for an entire nation

By Sally Robertson, B.Sc.Mar 26 2015

Researchers in Iceland have published the largest ever studies of whole-genome data and effectively deduced the genetic code of “an entire nation.”

The set of four papers, published in the journal Nature Genetics, demonstrate the power of the sequencing revolution as a tool for elucidating the causes of disease, diversity and evolution.

Shutterstock / Sergey Nivens

The studies, which were performed by a team called deCODE, combined whole-genome sequence data from over 100,000 Icelandic individuals with nation-wide family trees to present the most in-depth genetic profile ever assembled of a population using DNA technology.

Kari Stefansson, founder of deCODE and lead author of the papers said:

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.  We’re contributing to important tools for making more accurate diagnostics for rare diseases; finding new risk factors and potential drug targets for diseases like Alzheimer’s; and even showing how the Y chromosome, a loner in the paired world of our genome, repairs itself as it passes from father to son.

In the paper “Large scale whole-genome sequencing of the Icelandic population,” the authors show how nationwide genomic data can be used to impute even very rare sequencing information across a population to make new discoveries and improve the world of diagnostics.

The paper “Identification of a large set of rare complete human knockouts,” describes how the scale and depth of the deCODE data was used to identify over 1,000 knocked out genes in the population. At least one of these knocked-out genes was found in 8% of the104,000 individuals studied. By examining the health and other characteristics of these people, researchers should be able to identify the direct effects of particular genes on human health and establish ways of improving drugs and diagnostics.

Traditionally, genetic research has involved scientists identifying patients with a certain disease and then sifting through their genes to try and find mutations shared by the patients – mutations that may or may not be related to the disease. The approach described in this paper turns that model on its head.

“First you find individuals who are genetic outliers,” comments Daniel MacArthur, a researcher from the Broad Institute. “Then you pull back and look about what’s interesting or unusual about them.”

In the paper “The Y-chromosome point mutation rate in humans,” the researchers look at over 50,000 years of male lineage to assess the rate of mutation in the Y-chromosome. This rate provides a kind of evolutionary clock that can be used to date historical events in human evolution. The approach placed our most recent common ancestor as living 239,000 years ago, which is down almost 100,000 years from previous estimates suggesting this was 308,000 years ago.

Finally, the paper “Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease,” describes how the authors have found a gene linked to Alzheimer’s disease. This rare but powerful new risk factor has also been replicated in the US and in several European countries.

Stefansson says the studies show “how a small population such as ours, with the generous participation of the majority of its citizens, can advance science and medicine worldwide.”

“Other countries are now preparing to undertake their own large-scale sequencing projects, and I would tell them the rewards are great,” he adds.