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Melting pot or mosaic? International collaboration studies genomic diversity in Mexico

Melting pot or mosaic? International collaboration studies genomic diversity in Mexico

6626429111_df791cbb8d_zMexico is a vast country with a storied past. Indigenous Native American groups across the country maintain their own languages and culture, while its cosmopolitan residents of large cities are as globally connected as anywhere on Earth. But Mexicans and Mexican Americans are usually lumped together as “Latinos” for the purposes of genetic or medical studies.

Now an international collaboration headed by Stanford geneticist Carlos Bustamante, PhD, and the University of California, San Francisco pulmonologist and public-health expert Esteban Burchard, MD, MPH, has assessed the breadth and depth of genomic diversity in Mexico for the first time. Their work was published today in Science. As I explain in our release:

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.

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.

Surprisingly, this pattern of diversity is mirrored in the genomes of Mexican individuals with mixed heritage (usually a combination of European, Native American and African):

Consistent with the history of the Spanish occupation and colonization of Mexico, the researchers found that the European portion of the mixed-individuals’ genomes broadly corresponded to that of modern-day inhabitants of the Iberian Peninsula. The Native American portion of their genomes, however, was more likely to correspond to that of local indigenous people. A person in the Mexican state of Sonora, for example, was likely to have ancestors from indigenous groups in the northern part of the country, whereas someone from Yucatan was more likely to have a southern native component in their genome, namely Mayan.

“We were really fascinated by these results because we had expected that 500 years of population movements, immigration and mixing would have swamped the signal of pre-Columbian population structure,” said Bustamante

Finally, the researchers found that the origin of the Native America portion of an individual’s genome affected a clinical measure of lung function abbreviated FEV1:

The researchers drew on data that calculated the predicted normal FEV1 for each subject based on age, gender, height and ethnicity (in this case, the reference was a standard used for all people of Mexican descent). To understand implications of these results within Mexico, they modeled the predicted lung function across Mexico, accounting for differences in local Native American ancestry for a large cohort of mestizos from eight states. The model predicts a marked difference across the country, with the average predicted FEV1 for a person from the northern state of Sonora and another from the state of Yucatan differing by about 7.3 percent. (That is, the population from Sonora has predicted values that were slightly higher than the average for the country, and those from the Yucatan were slightly lower.)

“There’s a definite predicted difference that’s due only to an individual’s Native American ancestry,” said Gignoux. “Variations in genetic composition clearly give a different physiological response.”

The researchers emphasize that a lower FEV1 does not necessarily mean a particular ethnic group has impaired lung function. Disease analysis takes place in the context of standardized values of matched populations, and the study points out how it is necessary to match people correctly to their ethnic backgrounds before making clinical decisions.

Stanford’s Andres Moreno Estrada, MD, PhD, and Christopher Gignoux, PhD, share first authorship of the study with Juan Carlos Fernandez Lopez, a researcher at Mexico’s National Institute of Genomic Medicine.

Previously: Roots of disease may vary with ancestry, according to Stanford geneticist, Recent shared ancestry between southern Europe and North Africa identified by Stanford researchers, and Caribbean genetic diversity explored by Stanford/University of Miami researchers
Photo by DL

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