A New Mobile App or Genomic Understanding?

Eyjafjallajökull

Silicon Valley has been a tremendous incubator for some of most our recent inventions: the first integrated transistor chip, which led to Intel; the first true personal computer, which led to Apple. Yet, this esteemed venture capital (VC) community now seems to need a self-medication of innovation. Aren’t we all getting a little jaded from yet another “new, great mobile app” — worth in the tens of billions (but having no revenue model) — courtesy of a bright and young group of 20-somethings?

It is indeed gratifying to see innovators, young and old, rewarded for their creativity and perseverance. Yet, we should be encouraging more of our pioneers to look beyond the next cool smartphone invention. Perhaps our technological and industrial luminaries and their retinues of futurists could do us all a favor if they channeled more of their speculative funds at longer-term and more significant endeavors: cost-effective desalination; cheaper medications; understanding and curing our insidious diseases; antibiotic replacements; more effective recycling; cleaner power; cheaper and stronger infrastructure; more effective education. These are all difficult problems. But therein lies the reward.

Clearly some pioneering businesses are investing in these areas. But isn’t it time we insisted that the majority of our private and public intellectual capital (and financial) should be invested in truly meaningful ways. Here’s an example from Iceland — with their national human genome project.

From ars technica:

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 for the 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 settlers—between 8 and 20 thousand, who arrived just 1100 years ago. It also has an unusually well-documented genealogical history, with information sometimes stretching all the way back to the initial settlement of the country. Combined with excellent medical records, it’s a 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 Genetics last Wednesday. The wealth of data allowed them to track down genetic mutations that are related to a number of diseases, 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 Alzheimer’s disease. Although previous research had established that a gene in this region was involved in Alzheimer’s, 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. It’s the most common cardiac arrhythmia condition, and it’s considered early-onset if it’s diagnosed before the age of 60. The researchers found eight Icelanders diagnosed with the condition, all carrying a mutation in the same gene, MYL4.

The studies also turned up a gene with an unusual pattern of inheritance. It causes increased levels of thyroid stimulation when it’s 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 aren’t 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 isn’t 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 for people who have genetic knockouts, and then examine their medical records to see how their missing genes affect their health. It’s 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.

The Icelandic data allowed the researchers to calculate what they suggest is a more accurate mutation rate, placing the father of all humans at around 239,000 years ago. This is the estimate with the greatest likelihood, but the full range falls between 174,000 and 321,000 years ago. This estimate places the paternal ancestor closer in time to the maternal ancestor.

Read the entire story here.

Image: Gígjökull, an outlet glacier extending from Eyjafjallajökull, Iceland. Courtesy of Andreas Tille / Wikipedia.