The immunogenetic diversity of the HLA system in Mexico correlates with underlying population genetic structure.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. We identified the presence of 4268 unique HLA extended haplotypes across Mexico and find that the ten most frequent (HF > 1%) HLA haplotypes with significant linkage disequilibrium (Δ'≥0.1) in Mexico (accounting for 20% of the haplotypic diversity of the country) are of primarily Native American ancestry (A*02~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*08~DQB1*04, A*68~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*14~DQB1*03:01, A*24~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*04~DQB1*03:02, A*02~B*40:02~DRB1*04~DQB1*03:02, A*68~B*35~DRB1*04~DQB1*03:02, A*02~B*15:01~DRB1*04~DQB1*03:02). Admixture estimates obtained by a maximum likelihood method using HLA-A/-B/-DRB1 as genetic estimators revealed that the main genetic components in Mexico as a whole are Native American (ranging from 37.8% in the northern part of the country to 81.5% in the southeastern region) and European (ranging from 11.5% in the southeast to 62.6% in northern Mexico). African admixture ranged from 0.0 to 12.7% not following any specific pattern. We were able to detect three major immunogenetic clusters correlating with genetic diversity and differential admixture within Mexico: North, Central and Southeast, which is in accordance with previous reports using genome-wide data. Our findings provide insights into the population immunogenetic substructure of the whole country and add to the knowledge of mixed ancestry Latin American population genetics, important for disease association studies, detection of demographic signatures on population variation and improved allocation of public health resources.

Genetic diversity of HLA system in two populations from Hidalgo, Mexico: Pachuca and rural Hidalgo.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 122 Mexicans from the state of Hidalgo living in the city of Pachuca (N = 41) and rural communities (N = 81), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in Hidalgo include eight Native American and one European haplotypes. Admixture estimates revealed that the main genetic components in Hidalgo are Native American (58.93 ±â€¯2.16% by ML; 54.51% of Native American haplotypes) and European (32.49 ±â€¯2.88% by ML; 28.69% of European haplotypes), and a relatively high African genetic component (8.58 ±â€¯0.93% by ML; 6.97% of African haplotypes).

Genetic diversity of HLA system in seven populations from Veracruz, Mexico: Veracruz city, Coatzacoalcos, Córdoba, Orizaba, Poza Rica, Xalapa and rural Veracruz.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1113 Mexicans from the state of Veracruz living in the cities of Coatzacoalcos (N = 55), Orizaba (N = 60), Córdoba (N = 56), Poza Rica (N = 45), Veracruz (N = 171), Xalapa (N = 187) and rural communities (N = 539) to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes include 12 Native American haplotypes. Admixture estimates revealed that the main genetic components are Native American (64.93 ±â€¯1.27% by ML; 55.10% of Native American haplotypes) and European (26.56 ±â€¯0.89% by ML; 28.38% of European haplotypes), and a relatively high African genetic component (8.52 ±â€¯1.82% by ML; 8.78% of African haplotypes).

Genetic diversity of HLA system in two populations from Oaxaca, Mexico: Oaxaca city and rural Oaxaca.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 636 Mexicans from the state of Oaxaca living in the city of Oaxaca (N = 151) and rural communities (N = 485), to obtain information regarding allelic and haplotypic frequencies. We found that the 13 most frequent haplotypes in Oaxaca are all of putative Native American origin. Admixture estimates revealed that the main genetic components in the state of Oaxaca are Native American (73.12 ±â€¯2.77% by ML; 61.52% of Native American haplotypes) and European (17.36 ±â€¯2.07% by ML; 20.69% of European haplotypes), and a relatively high African genetic component (9.52 ±â€¯0.88% by ML; 8.94% of African haplotypes).

Genetic diversity of HLA system in two populations from Puebla, Mexico: Puebla city and rural Puebla.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 2827 Mexicans from the state of Puebla living in the city of Puebla (N = 1994) and rural communities (N = 833), to obtain information regarding allelic and haplotypic frequencies. We found that the 16 most frequent haplotypes in Puebla are all of them Native American. Admixture estimates revealed that the main genetic components in the state of Puebla are Native American (72.21 ±â€¯1.25% by ML; 63.30% of Native American haplotypes) and European (21.05 ±â€¯1.92% by ML; 23.86% of European haplotypes), and a less prominent African genetic component (6.74 ±â€¯2.20% by ML; 6.20% of African haplotypes).

Genetic diversity of HLA system in two populations from Tlaxcala, Mexico: Tlaxcala city and rural Tlaxcala.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1011 Mexicans from the state of Tlaxcala residing in the city of Tlaxcala (N = 181) and rural communities (N = 830), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes in Tlaxcala are all of Native American origin. Admixture estimates revealed that the main genetic components are Native American (75.13 ±â€¯1.56% by ML; 69.24% based on of Native American haplotypes) and European (16.10 ±â€¯4.98% by ML; 19.74% of European haplotypes), with a less prominent African genetic component (8.78 ±â€¯4.09% by ML; 4.35% of African haplotypes).

Genetic diversity of HLA system in six populations from Mexico City Metropolitan Area, Mexico: Mexico City North, Mexico City South, Mexico City East, Mexico City West, Mexico City Center and rural Mexico City.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 1217 Mexicans from the Mexico City Metropolitan Area living in the northern (N = 751), southern (N = 52), eastern (N = 79), western (N = 33), and central (N = 152) Mexico City, and rural communities (N = 150), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes include 11 Native American haplotypes. Admixture estimates revealed that the main genetic components are Native American (63.85 ±â€¯1.55% by ML; 57.19% of Native American haplotypes) and European (28.53 ±â€¯3.13% by ML; 28.40% of European haplotypes), and a less apparent African genetic component (7.61 ±â€¯1.96% by ML; 7.17% of African haplotypes).