2,636 Icelandic genomes pinpoint risk for Alzheimers, other diseases

'Dialogue' by Anna Leoniak and Fiann Paul, a 2008 Reykjavk Arts Festival exhibit featuring photographs of children from Icelandic rural areas.

An Icelandic genetics firm has sequenced the genomes of 2,636 of its countrymen and women, finding genetic markers for a variety of diseases, as well as a new timeline forthe paternal ancestor of all humans.

Iceland is, in many ways, perfectly suited to being a genetic case study. It has a small population with limited genetic diversity, a result of the population descending from a small number of settlersbetween 8 and 20 thousand, who arrived just 1100 years ago.It also has an unusually well-documented genealogical history, with informationsometimes stretching all the way back to the initial settlementof the country. Combined with excellent medical records, it'sa veritable treasure trove for genetic researchers.

The researchers at genetics firm deCODE compared the complete genomes of participants with historical and medical records, publishing their findings in a series of four papers in Nature Geneticslast Wednesday. The wealth of data allowed them to track down genetic mutations that are related to a number ofdiseases, some of them rare. Although few diseases are caused by a single genetic mutation, a combination of mutations can increase the risk for certain diseases. Having access to a large genetic sample with corresponding medical data can help to pinpoint certain risk-increasing mutations.

Among their headline findings was the identification of the gene ABCA7 as a risk factor for Alzheimers disease. Although previous research had established that a gene in this region was involved in Alzheimers, this result delivers a new level of precision. The researchers replicated their results in further groups in Europe and the United States.

Also identified was a genetic mutation that causes early-onset atrial fibrillation, a heart condition causing an irregular and often very fast heart rate. Its the most common cardiac arrhythmia condition, and its considered early-onset if its diagnosed before the age of 60. The researchers found eight Icelanders diagnosed with the condition, all carrying a mutation inthe same gene,MYL4.

The studiesalso turned up a gene with an unusual pattern of inheritance. Itcauses increased levels of thyroid stimulation when its passed down from the mother, but decreased levels when inherited from the father.

Genetic research in mice often involves knocking out or switching off a particular gene to explore the effects. However, mouse genetics arent a perfect approximation of human genetics. Obviously, doing this in humans presents all sorts of ethical problems, but a population such as Iceland provides the perfect natural laboratory to explore how knockouts affect human health.

The data showed that eight percent of people in Iceland have the equivalent of a knockout, one gene that isnt working. This provides an opportunity to look at the data in a different way: rather than only looking for people with a particular diagnosis and finding out what they have in common genetically, the researchers can look forpeople who have genetic knockouts, and then examine their medical records to see how their missing genes affect their health. Its then possible to start piecing together the story of how certain genes affect physiology.

Finally, the researchers used the data to explore human history, using Y chromosome data from 753 Icelandic males. Based on knowledge about mutation rates, Y chromosomes can be used to trace the male lineage of human groups, establishing dates of events like migrations. This technique has also been used to work out when the common ancestor of all humans was alive. The maternal ancestor, known as Mitochondrial Eve, is thought to have lived 170,000 to 180,000 years ago, while the paternal ancestor had previously been estimated to have lived around 338,000 years ago.

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2,636 Icelandic genomes pinpoint risk for Alzheimers, other diseases