Early human history was characterized by many rapid, long-distance migrations. But despite our beginnings as travelers, genetic evidence published online last Sunday in Nature indicates that after expanding to all corners of the earth people (at least those in Europe) tended to stay close to home.

Close on the heels of similar research published just a few weeks ago (and covered in The Spittoon), John Novembre and colleagues have created a genetic “map” of Europe that closely mirrors the geographic map. Their results will allow scientists to better understand how geography contributes to genetic variation, which is important for both genome-wide association studies and ancestry analyses.

Figure 1: The genetic map of Europe using PCA, with the geographic map of Europe for reference. Figure 2: The same map, but zoomed in on Switzerland. Swiss individuals tend to cluster with countries that speak the same language. (Courtesy: John Novembre, UCLA)

The researchers used a mathematical technique called principle components analysis (PCA) to collapse large amounts of SNP data for 3,192 people drawn from throughout Europe into a two-dimensional “map” of their genetic distances from one another. (Figure 1)

When the researchers looked at the DNA of any two individuals, they found that the number of genetic differences between them was proportional to the geographic distance that separates their respective home countries. Even within countries the researchers saw that groups with similar cultural histories shared similar genetics. For example, Italian-speakers from southern Switzerland tended to cluster together with other Italian-speakers and apart from other Swiss groups. (Figure 2)

Using only genetic data, the researchers were able to assign, on average, 50% of European individuals to within 400 kilometers of their correct country of origin. But there was one caveat: all four grandparents of an individual had to come from the same European country for the assignment to be correct. People with mixed European ancestry tended to show up between the locations of their ancestors.

The accuracy of assignment varied greatly from country to country: some people, like the Swedes and Portuguese, were placed on the map with less precision than other groups like the Polish and Belgians.

As in earlier research that constructed a genetic map of Europe, the results of this study show that genetic variations between people tend to follow a northwest to southeast path. This may reflect an ancient migration after the Last Ice Age when glacial sheets extended down from northern Europe. Human groups (not to mention grasshoppers, hedgehogs, etc.) were forced to take refuge in warm southern locations like the Italian and Iberian Peninsulas. But after the glaciers melted about 15,000 years ago, humans began to re-colonize Europe, moving from south to north.

In the past, genome-wide association studies have been hampered by the effects of geography on genetics. For example, a study looking for DNA variants associated with height found spurious evidence of linkage to SNPs that are actually linked to lactose tolerance, because both traits vary along the same NW/SE axis in Europe. The results of this study current study and others like it will help scientists make corrections in their data and increase their ability to detect true associations.

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Dogs suffer from a number of inherited eye conditions; the progression of their symptoms and gradual vision loss have been found to mirror various similar disorders in humans. One example: cone-rod dystrophies, which rob humans and dogs of their vision by destroying both the cone cells that pick out images and colors in bright light and the rod cells, which work best under low lighting conditions.

Norwegian and Swedish researchers have used a genome-wide approach to identify a genetic mutation in standard wire-haired dachsunds that is responsible for early onset cone-rod dystrophy, known as CRD. Their results, published online today in the journal Genome Research, could help researchers studying similar cone-rod disorders in humans to find the genetic basis of those conditions. About one person in 40,000 is affected by a form of cone-rod dystrophy.

The team used a family of dachshunds, several of whom had CRD. Lingaas and his colleagues used a genome-wide analysis approach on 26 full- and half-siblings, studying nearly 50,000 gene variants much the same way 23andMe uses an array of gene variants to analyze customer DNA. They studied the dogs in sibling pairs — where one litter mate had CRD and the other had normal vision — to find out what genetic differences might be responsible for the eye condition.

The researchers narrowed their focus to four candidate genes, and ultimately identified a deletion in part of the NPHP4 gene as the cause of the dogs’ blindness.

“This [NPHP4] gene has been associated with a combination of kidney and eye disease in human patients,” said lead researcher Frode Lingaas in a statement. “Here, we found a mutation that affects only the eyes, suggesting that this gene might be a candidate for human patients with eye disease only.”

Gene therapy treatments based on other associations have already been tried in dogs with cone-rod dystrophies. Researchers hope such treatments could some day be applied to similar conditions in humans.

“Assuming that NPHP4 has the same function in humans and dogs,” Lingaas and his colleagues added in their paper, “it will now be interesting to search for mutations in NPHP4 in human CRD patients without kidney disease.”

Image from: Frode Lingaas, Norwegian School of Veterinary Science

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