The genetics of Mexico recapitulates Native American substructure and affects biomedical traits

Abstract

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1,000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between sub-continental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

“…The Mexican population also harbors great ethnic diversity [108] as confirmed by numerous studies on the admixture in Mexico. Amerindian ancestry is the largest component (0.51-0.56) in the general population, followed by European (0.40-0.45), while the African component is small (0.02-0.05).…”

The Genetic Diversity of the Americas

“…A simple explanation for this observation was that of a genetic continuity between local pre-and post-Columbian populations (i.e., that the native population could have become amalgamated into the growing admixed population from that region). Subsequent autosomal marker surveys [including high-density singlenucleotide polymorphism (SNP) haplotype analyses] in populations from Central and South America have consistently shown that the native ancestry of these populations relates most closely to natives living in proximity (3,61,62,106). These observations suggest that, despite an increased migration across Ibero-America in recent decades, this has not been extensive enough to erase the signature of pre-Columbian native population structure.…”

The complex genetics of human insulin-like growth factor 2 are not reflected in public databases

“…Moreover, they are not found in GTEx except in liver, where expression levels are very low (≤ 1 TPM for each of 4 mRNA species). In addition, since the genetics of Mexico are very complicated, with region-specific sub-groups being identified (75), it is likely that the MAF of 0.17 identified in the study cohort (38) will vary significantly among different populations of Mexican origin once a larger and more thorough genetic analysis is completed.…”