Exploring the ancestry and admixture of Mexican Oaxaca Mestizos from Southeast Mexico using next-generation sequencing of 11 HLA loci

Abstract

The Mestizos of Oaxaca resulted from the admixture of Zapotecan Natives with Spaniards and Africans. We selected 112 donors from Oaxaca and applied next-generation sequencing to characterize exon and intron variants in complete or extended HLA genes. Some alleles found, are unique to Mexican Natives and most likely will be absent in most major ethnicities, namely: Caucasians, Africans or Asians. Among these are HLA-A*68:03:01, HLA-A*68:05:01, HLA-C*03:04:01:02, HLA-C*15:09, HLA-C*3:05, HLA-C*03:06:01, HLAB*39:05:01, HLA-B*35:14:01, HLA-B*35:12:01, HLA-B*35:43:01, HLA-B*40:05, HLA-B:40:08, HLA-B*51:02:01, HLA-B*35:24:01 and HLA-B*39:08. HLA-DQA1*05:05:01:05 and some HLA-DRB1 alleles were only present in Amerindians/Mestizos. Three haplotypes are unique to Mexican Natives, five to Middle-Eastern and Sephardi-Jews. We detected a novel HLA-DQA1*04:01:01 exon 4 variant. Any novel allele may have been positively selected to enlarge the peptide-binding repertoire, and some, like HLA-B*39:02:02 and HLA-B*39:05:01 were found with unique haplotype associations, suggesting convergent evolution events and/or allele lineage diversification. The allele frequencies were fairly evenly distributed in most HLA loci with the exception of HLADPB1. The application of NGS in Oaxaca is novel and will lead to better use in the clinical setting. It offers deep knowledge on the population structure, origins, migration, and discovery of new alleles and haplotypes that other techniques did not achieve.

The polymorphism of HLA‐A, ‐C, ‐B, ‐DRB3/4/5, ‐DRB1, ‐DQB1 loci in Zhejiang Han population, China using NGS technology

“…Other reports showed DRB4*01:03 and DRB3*02:02 were the most common alleles in population of Korea (Song et al., 2002), DRB4*01:01 and DRB3*02:02 were the most common alleles in Japanese (Kojima et al., 2000). However, HLA‐DRB4*01:01 and HLA‐DRB4*01:03 were the most common in the native Americans (Barquera et al., 2020), but HLA‐DRB4*01:03:01 and HLA‐DRB3*01:01:02 were common in European Americans and Mexicans (Creary et al., 2019; González‐Quezada et al., 2019 ). The data of more than 1300 samples from Germany, Malta, India, Iran, Japan and Korea and African American ancestry showed that the HLA‐DRB3*02:02 and HLA‐DRB4*01:03 were the most common alleles in population of Germany, India, Iran, Korea and Malta (Degenhardt et al., 2019).…”

Variability in Susceptibility to Type I Interferon Response and Subgenomic RNA Accumulation Between Clinical Isolates of Dengue and Zika Virus From Oaxaca Mexico Correlate With Replication Efficiency in Human Cells and Disease Severity

“…Characterization of the transmissibility and virulence phenotype of the Flavivirus variants that circulate in the Mexican population could provide invaluable information on the selection dynamic as well as the variability of natural susceptibility of the hosts since available evidence suggests that genetic variability in Mexicans is particular in comparison with other Latin American populations and could influence biomedical treats ( Moreno-Estrada et al., 2014 ). This is especially true for the Oaxaca population, as it is characterized by diverse Amerindian groups admixed with Mediterranean and African genetic backgrounds and features high diversity of HLA ( González-Quezada et al., 2019 ). The Flavivirus variants that cocirculate in the Mexican population could be subjected to characteristic selection pressures; more multidisciplinary studies that could identify genetic traits that select successful Flavivirus variants that dominate the epidemiologic picture should be conducted.…”

Genome-wide association study reveals an association between the HLA-DPB1∗02:01:02 allele and wheat-dependent exercise-induced anaphylaxis

“…Our control group allele frequency was comparable with that (0.228) in a different general Japanese population cohort (n ¼ 1,120), 29 indicating that our targeted sequencing approach was appropriate. The HLA-DPB1*02:01:02 allele frequency is 0.140, 0.138, 0.103, and 0.361, in Chinese, 30 European American, 31 Mexican, 32 and Spanish populations, 33 respectively. In almost all populations, this allele has the second or third highest frequency, suggesting that it may be used globally as a WDEIA-risk biomarker.…”