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 Nuevo León, Mexico: Monterrey and rural Nuevo León.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 665 Mexicans from the state of Nuevo León living in the city of Monterrey (N = 226) and rural communities (N = 439), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Nuevo León include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nuevo León are Native American (54.53 ±â€¯0.87% by ML; 48.88% of Native American haplotypes) and European (38.67 ±â€¯4.06% by ML; 32.59% of European haplotypes), and a less prominent African genetic component (6.80 ±â€¯4.30% by ML; 8.26% of African haplotypes).

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

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 479 Mexicans from the state of Durango living in Durango city (N = 153) and rural communities (N = 326), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Durango include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in Durango are European (54.34 ±â€¯1.68%) and Native American (45.66 ±â€¯2.24%), while African genetic component was virtually absent (0.00 ±â€¯2.03%). However, African haplotypes could be estimated at a proportion of 9.13%.

Genetic diversity of HLA system in three populations from Chihuahua, Mexico: Chihuahua City, Ciudad Juárez and rural Chihuahua.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 461 Mexicans from the state of Chihuahua living in Chihuahua city (N = 119), Ciudad Juárez (N = 106) and rural communities (N = 236), to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes found in the state of Chihuahua include seven Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in Chihuahua are European (52.12 ±â€¯0.88% by ML; 41.53% of European haplotypes) and Native American (39.51 ±â€¯2.17% by ML; 37.45% of Native American haplotypes), while African genetic component was less apparent (8.36 ±â€¯1.47% by ML; 11.70% of African haplotypes).

Genetic diversity of HLA system in a population sample from Aguascalientes, Mexico.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 95 Mexicans from the state of Aguascalientes to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes in the state of Aguascalientes include four Native American, three European and one Asian haplotypes. Admixture estimates revealed that the main genetic components in the state of Aguascalientes are Native American (54.53 ±â€¯3.22% by ML; 44.21% of Native American haplotypes) and European (44.34 ±â€¯0.45% by ML; 40.53% of European haplotypes), and a relatively low African genetic component (1.13 ±â€¯2.33% by ML; 5.26% of African haplotypes).

Genetic diversity of HLA system in two populations from Tamaulipas, Mexico: Ciudad Victoria and rural Tamaulipas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 148 Mexicans from the state of Tamaulipas living in Ciudad Victoria (N = 23) and rural communities (N = 125), to obtain information regarding allelic and haplotypic frequencies. We found that the most frequent haplotypes in the state of Tamaulipas include ten Native American, three European and one African haplotypes. Admixture estimates revealed that the main genetic components in the state of Tamaulipas are Native American (54.69 ±â€¯0.93% by ML; 47.65% of Native American haplotypes) and European (34.66 ±â€¯5.62% by ML; 33.56% of European haplotypes), and a relatively high African genetic component (10.65 ±â€¯5.05% by ML; 12.42% of African haplotypes).

Genetic diversity of HLA system in two populations from San Luis Potosí, Mexico: San Luis Potosí City and rural San Luis Potosí.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 117 Mexicans from the state of San Luis Potosí living in the city of San Luis Potosí (N = 30) and rural communities (N = 87), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state include 13 Native American, six European, two African and two Asian haplotypes. Admixture estimates revealed that the main genetic components are Native American (52.72 ±â€¯0.66% by ML; 48.29% of Native American haplotypes) and European (34.62 ±â€¯4.28% by ML; 32.48% of European haplotypes), and a relatively high African genetic component (12.66 ±â€¯4.61% by ML; 10.26% of African haplotypes).

Genetic diversity of HLA system in three populations from Coahuila, Mexico: Torreón, Saltillo and rural Coahuila.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 684 Mexicans from the state of Coahuila living in Saltillo (N = 72), Torreón (N = 396) and rural communities (N = 216), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Coahuila include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Coahuila are European (49.72 ±â€¯4.18% by ML; 37.49% of European haplotypes) and Native American (45.01 ±â€¯2.69% by ML; 42.98% of Native American haplotypes), while African genetic component is less apparent (5.27 ±â€¯1.88% by ML; 9.92% of African haplotypes).

Genetic diversity of HLA system in three populations from Zacatecas, Mexico: Zacatecas city, Fresnillo and rural Zacatecas.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 453 Mexicans from the state of Zacatecas living in Zacatecas city (N = 84), Fresnillo (N = 103) and rural communities (N = 266) to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes for the state of Zacatecas include seven Native American most probable ancestry (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02; A*02 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04; A*24 ∼ B*39 ∼ DRB1*14 ∼ DQB1*03:01; A*02 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*24 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*68 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02 and A*24 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04) and two European MPA haplotypes (HLA ∼ A*01 ∼ B*08 ∼ DRB1*03:01 ∼ DQB1*02 and A*29 ∼ B*44 ∼ DRB1*07 ∼ DQB1*02). Admixture estimates revealed that the main genetic components in the state of Zacatecas are European (47.61 ±â€¯1.85%) and Native American (44.74 ±â€¯1.12%), while the African genetic component was less apparent (7.65 ±â€¯1.12%). Our findings provide a starting point for the study of population immunogenetics of urban and rural populations from the state of Zacatecas and add to the growing knowledge on the population genetics of Northern Mexico.