The first large-scale, comprehensive analysis of the genomic diversity of Mexico — led by researchers at the Stanford University School of Medicine, the University of California-San Francisco and the Mexican National Institute of Genomic Medicine — has identified a dazzling mosaic of genotypes and population substructures across the country.

Some groups are as genetically different from one another as Europeans are from East Asians.

The study, published June 13 in Science, soundly refutes the current practice of lumping together Mexicans or Latinos as a homogenous group for genetic, clinical or population studies. In particular, the researchers found that variations in Native American ancestry among Mexicans and Mexican Americans significantly affect biomedical traits, such as lung function, emphasizing the importance of incorporating fine-scale ethnic information into clinical practice.



The analysis represents an international collaboration of researchers from the United States, Mexico, Spain and the United Kingdom.



How it affects health

“Understanding the genetic structure of a population is important for understanding its population history, as well as designing studies of complex biomedical traits, including disease susceptibility,” said Stanford professor of genetics Carlos Bustamante, PhD. “As we deploy genomics technology in previously understudied populations like those of Latin America, we discover remarkable richness in the genetic diversity of these important groups and why it matters for health and disease.”



“Mexico harbors one of the largest amounts of pre-Columbian genetic diversity in the Americas,” said Andres Moreno-Estrada, MD, PhD, life sciences research associate at Stanford. “For the first time, we’ve mapped this diversity to a very fine geographic scale, and shown that it has a notable physiological impact on an important clinical trait: lung function.”

We’re moving beyond blanket definitions like Mexican or Latino.

Bustamante, who directs the Stanford Center for Computational, Evolutionary and Human Genomics, shares senior authorship of the study with Esteban Burchard, MD, MPH, professor of bioengineering and therapeutic sciences and medicine at UCSF. Moreno shares lead authorship with Christopher Gignoux, PhD, a postdoctoral scholar now at Stanford and previously at UCSF, and Juan Carlos Fernandez Lopez, a researcher at the Mexican genomic institute.

Burchard noted that in lung diseases, such as asthma or emphysema, a person’s ancestry at specific locations on their genes matters. “In this study, we realized that for disease classification it also matters what type of Native American ancestry you have,” he said.

The researchers compared variation in more than 1 million single nucleotide polymorphisms, or SNPs, among 511 people representing 20 indigenous populations from all over Mexico. They compared these findings with SNP variation among 500 people of mixed Mexican, European and African descent (a category called mestizos) from 10 Mexican states, a region of Guadalajara and Los Angeles, as well as with SNP variation among individuals from 16 European populations and the Yoruba people of West Africa.

As different as Europeans and Chinese

The researchers found that Mexico’s indigenous populations diverge genetically along a diagonal northwest-to-southeast axis, with differences becoming more pronounced as the ethnic groups become more geographically distant from one another. In particular, the Seri people along the northern mainland coast of the Gulf of California and a Mayan people known as the Lacandon found near the country’s southern border with Guatemala are as genetically different from one another as Europeans are from Chinese.

“Many of these Native American groups have been and remain very geographically isolated,” said Gignoux. “We found they share very little genetically with other neighboring groups.” When rare gene flow did occur, it was concentrated among populations on the country’s coastlines, the researchers found.

Much of Mexico, however, is populated by people of mixed ancestry, primarily as a result of European colonization. The researchers found that these individuals had a large amount of European and Native American ancestry, coupled with a relatively small amount (5 percent or less) of African ancestry.

“Because this mixing happened fairly recently within the spectrum of human history,” said Gignoux, “we can use genomic data techniques to identify which segments of an individual’s genome correspond to specific ancestral populations. What portion comes from Europe? What from Native Americans? And then we can find out how that fits into the pattern of modern-day populations.”