Imagine if people from Kansas and California were as genetically distinct from each other as someone from Germany is from someone from Japan. That’s the kind of remarkable genetic variation that scientists have now found within Mexico, thanks to the first fine-scale study of human genetic variation in that country. This local diversity could help researchers trace the history of the country’s different indigenous populations and help them develop better diagnostic tools and medical treatments for people of Mexican descent living all over the world.The team has done a “tremendous job” of creating a “blueprint of all the genetic diversity in Mexico,” says Bogdan Pasaniuc, a population geneticist at the University of California (UC), Los Angeles, who was not involved in the research.Mexico contains 65 different indigenous ethnic groups, 20 of which are represented in the study, says Andrés Moreno-Estrada, a population geneticist at Stanford University in Palo Alto, California, and the study’s lead author. Working with Carlos Bustamante, another Stanford population geneticist, the team sampled the genomes of indigenous populations all over Mexico, from the northern desert of Sonora to the jungles of Chiapas in the south. Over centuries of living so far apart—and often in isolation because of mountain ranges, vast deserts, or other geographic barriers—these populations developed genetic differences from one another, Bustamante explains. Many of these variants are what he calls “globally rare but locally common.” That is, a genetic variant that’s widespread in one ethnic group, like the Maya, may hardly ever show up in people of different ancestry, like people of European descent. If you study the genomes of only the Europeans, you’d never catch the Maya variant. And that’s a big problem for people with Maya ancestry if that variant increases their risk of disease or changes the way they react to different kinds of medication. “All politics is local, right? 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The most divergent indigenous groups in Mexico are as different from each other as Europeans are from East Asians, they report online today in Science. This diversity maps onto the geography of Mexico itself. The farther away ethnic groups live from each other, the more different their genomes turn out to be.But most people in Mexico or of Mexican descent these days are not indigenous but rather mestizo, meaning they have a mixture of indigenous, European, and African ancestry. Do their genomes also vary by what region of Mexico they come from, or has all that local variation been smoothed out by centuries of different groups meeting, mixing, and having babies?To answer that question, the team collaborated with Mexico’s National Institute of Genomic Medicine, which has been collecting genetic data from mestizos for many years. Somewhat surprisingly, they found that mestizos in a given part of Mexico tended to have the same “rare” genetic variants as their indigenous neighbors. The mestizo genomes “track so well with the indigenous groups that we could use the genetic diversity in mestizos to make inferences about [their native] ancestors,” Pasaniuc says. Strong genetic markers of Maya ancestry, for example, show up in the genomes of modern people living in the Yucatán Peninsula and the northern part of Mexico’s Gulf Coast in the modern state of Veracruz, which likely reflects a pre-Columbian Maya trade or migration route. “It gives us a historical understanding of what these populations have been up to,” says Christopher Gignoux, a postdoc in Bustamante’s group at Stanford.Even more important are the study’s clinical implications. To determine whether the genetic variation in Mexico could influence disease risk and the accuracy of diagnostic tools, Esteban Burchard, a pulmonologist at UC San Francisco, analyzed how a common measure of lung function tracks with Mexico’s genetic variation. He found that people with genetic variants common in the east of the country had different results on the lung function test than did people with variants from the west. That means doctors probably shouldn’t be using the same criteria to diagnose lung disease in both populations, he says. “What we demonstrated is that depending upon the type of Native American ancestry you have, it can dramatically influence the diagnosis of lung disease, in a good or a bad way,” Burchard explains.Lung function is just one example of the ways in which Mexico’s fine-scale genetic variation could be affecting disease and diagnosis, the team says. For Bustamante, this wealth of potential clinical applications made the study particularly exciting to be a part of. “Let’s move beyond the questions we tend to focus on in population genetics and really try to tackle how we’re going to think about translating this” in ways that modern people can benefit from.*Correction, 13 June, 11:28 a.m.: Mexico contains 65 different indigenous ethnic groups, not 55, as was previously reported. This has been corrected.