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Genetic diversity of HLA system in three populations from Zacatecas, Mexico: Zacatecas city, Fresnillo and rural Zacatecas
Human Immunology xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
Human Immunology journal homepage: www.elsevier.com/locate/humimm
Genetic diversity of HLA system in three populations from Zacatecas, Mexico: Zacatecas city, Fresnillo and rural Zacatecas Diana Iraíz Hernández-Zaragozaa,b,1, Héctor Delgado-Aguirrec,1, Rodrigo Barqueraa,d, ,1, Carmen Adalid-Sáinzc,1, Stephen Claytond,1, Abraham Lona-Sáncheza, Liliana González-Medinaa, Hanna Pacheco-Ubaldoa, Alicia Bravo-Acevedoe, Néstor Escareño-Montielf, Javier Morán-Martínezg, Marisela del Rocío González-Martínezh, Yolanda Jaramillo-Rodríguezi, ⁎ ⁎ ⁎ Federico Juárez-de la Cruzf, Joaquín Zúñigaj,k, , Edmond Yunisl, , Carolina Bekker-Méndezm, , n,⁎ Julio Granados ⁎
a
Molecular Genetics Laboratory, Escuela Nacional de Antropología e Historia (ENAH), Mexico City, Mexico Immunogenetics Unit, Técnicas Genéticas Aplicadas a la Clínica (TGAC), Mexico City, Mexico c Laboratory of Histocompatibility, Unidad Médica de Alta Especialidad (UMAE) # 71, Instituto Mexicano del Seguro Social (IMSS), Torreón, Coahuila, Mexico d Department of Archaeogenetics, Max Planck Institute for the Science of Human History (MPI-SHH), Jena, Germany e Blood Bank, UMAE Hospital de Gineco Obstetricia No. 4 “Luis Castelazo Ayala”, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico f Department of Transplantation, Unidad Médica de Alta Especialidad (UMAE) # 71, Instituto Mexicano del Seguro Social (IMSS), Torreón, Coahuila, Mexico g Cellular Biology and Ultra Structure Department, Biomedical Research Center, Universidad Autónoma de Coahuila, Torreón, Coahuila, Mexico h Microbiology Department, Faculty of Medicine, Universidad Autónoma de Coahuila, Torreón, Coahuila, Mexico i Health Research Division, Unidad Médica de Alta Especialidad (UMAE) # 71, Instituto Mexicano del Seguro Social (IMSS), Torreón, Coahuila, Mexico j Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico k Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico l Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA m Immunology and Infectology Research Unit, Infectology Hospital, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico n Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ), Mexico City, Mexico b
ARTICLE INFO
ABSTRACT
Keywords: HLA Immunogenetics Population genetics Zacatecas Admixture
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 ± 1.85%) and Native American (44.74 ± 1.12%), while the African genetic component was less apparent (7.65 ± 1.12%). Our findings provide a starting point for the study of
Abbreviations: HLA, Human Leukocyte Antigen; MPA, Most-probable ancestry; LD, Linkage Disequilibrium ⁎ Corresponding authors at: Department of Archaeogenetics, Max Planck Institute for the Science of Human History. Kahlaische Strasse 10, 07745 Jena, Germany (R. Barquera). Laboratory of Immunobiology and Genetics, Research Division, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calz. De Tlalpan 4502, Bellisario Domínguez Sección XVI, 14080, Tlalpan, Mexico City, Mexico (J. Zúñiga). Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney St. #1234, Boston, MA 02215, USA (E. Yunis). Immunology and Infectology Research Unit, Infectology Hospital, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Calzada Vallejo y Jacarandas S/N Colonia La Raza, 02990 Mexico City, Mexico (C.B. Méndez). Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ), Vasco de Quiroga 15, Belisario Domínguez Sección XVI, 14080 Tlalpan, CDMX, Mexico (J. Granados). E-mail addresses: [email protected] (R. Barquera), [email protected] (J. Zúñiga), [email protected] (E. Yunis), [email protected] (C. Bekker-Méndez), [email protected] (J. Granados). URLs: http://www.shh.mpg.de/en (R. Barquera), http://www.iner.salud.gob.mx (J. Zúñiga), http://www.dana-farber.org (E. Yunis), http://www.cienciaimss.org/uim-en-inmunologia-e-infectologia/ (C. Bekker-Méndez), http://www.innsz.mx (J. Granados). 1 These authors contributed equally to the present work. https://doi.org/10.1016/j.humimm.2019.01.007 Received 10 December 2018; Received in revised form 22 January 2019; Accepted 23 January 2019 0198-8859/ © 2019 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.
Please cite this article as: Hernández-Zaragoza, D.I., Human Immunology, https://doi.org/10.1016/j.humimm.2019.01.007
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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.
Zacatecas is located in the northern part of Mexico (Fig. 1), bordering with the states of Durango, Coahuila, Nuevo Leon, San Luis Potosi, Guanajuato, Jalisco and Nayarit. Of the 58 municipalities that make up the state by 2010 [1], 14% of the population lived in the municipality of Fresnillo, making it the most populated municipality in the state. This is the region from where the largest number of samples was collected. As in the rest of the country, the pattern of settlement in Zacatecas is characterized by a high dispersion across hundreds of locations paired with high demographic density in few urban centers [2]. In Zacatecas there are about 20 native languages, although only 0.3% of the population over 3 years of age speak an indigenous language, of which the first 5 places in percentage of speakers to 2015 are: Huichol (27.4%), Nahuatl (17.1%), southern Tepehuan (15%), Mazahua (5.56%) and Mixtec (4.46%) [1]. The territory that currently comprises the state of Zacatecas has been inhabited at least since the Classic period by the Chalchihuites, a social group that settled mainly in three large complexes: Suchil, Alta Vista and Guadiana (in Durango) who were engaged in agriculture and mineral extraction. This occupation continued until the Post Classic period, but there is no indication that it survived until the period of contact with Europeans [3,4]. Upon the arrival of the European conquerors, northern Mexico was known as the “Great Chichimeca” territory and was inhabited by groups of hunter-gatherers hostile to the Aztec empire. The settlement of mines, mostly for silver, was the main reason for Spanish companies to undertake the conquest and colonization of this territory, aided by the displacement of Purépecha and Otomí population mainly from 1548 onwards [4], and through the Colonial period also Tlaxcaltecans, Cholultecs and Tarascans [5]. Also during the Colonial period, the arrival of African enslaved individuals for working in the mines was constant, because like in the mines in Guanajuato and San Luis, there was not enough manpower for the extraction of metals, the indigenous population was in decline and did not represent profits for the encomenderos [6]. Throughout the first years of Independent Mexico, the situation in Zacatecas went into crisis, as many settlements were abandoned and most of the mines were closed. But with the coming to power of Porfirio Díaz, in 1877, Mexico undertook the process of modernization. Díaz ruled Mexico for more than three decades, pacified the country and achieved the development of its economy. At the end of the 19th century, as the enclave economy developed, Mexico needed cheap labor to work in the mines and build railroads. It was planned to recruit a large contingent of Chinese workers in the USA to work in Mexico. On December 14th, 1899, representatives of both governments officially signed the Treaty of Friendship, Commerce and Navigation between China and Mexico in Washington. In this way, the two countries formally established diplomatic relations [7] which allowed the entry of Chinese workers into the state as workforce for the construction of the railway lines. The twentieth century was defined by a population growth paired with rejuvenation along with an increase in the emigration to the US. By 1970, 5% of the national population lived in Zacatecas; however, the population growth of the state has been decreasing (with the natural growth being always below the national average since the 1970’s [2]) and, together with the lack of economic development opportunities and low economic growth that forced migrating not only to other states but also to the United States, it currently represents only 1.3% of the national population [1,2]. Forty one percent of the population lives in rural areas, while the rest lives in cities such as Fresnillo (the most populated one) and Zacatecas (the capital city) [1]. Only 0.3% of the population is considered Native American, one of the lowest proportions for the whole country [1].
For the present work, we analyzed HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) PCR-SSP based typings in 453 Mexicans from the state of Zacatecas [the state of Zacatecas data is composed by the following populations: Mexico Zacatecas, Zacatecas city (N = 84, Allele Frequencies Net Database Identifier (AFND-ID): 3511), Mexico Zacatecas, Fresnillo (N = 103, AFND-ID: 3510), Mexico Zacatecas Rural (N = 266, AFND-ID: 3577)]. Briefly, genomic DNA was extracted from peripheral blood using standardized procedures (DNA Isolation Kit for Mammalian Blood, Roche Diagnostics, Basel, Switzerland; automated DNA extraction with the MagNA Pure Compact System, Roche Molecular Systems, Pleasanton, CA, USA; inhouse validated salting out techniques), and DNA was adjusted to a final concentration of 80–120 ng/μL and stored at –20 °C until use. HLA genotyping was performed using commercially available PCR sequence-specific primers (PCR-SSP) kits (AB/DR/DQ SSP Unitray®, Life Technologies/ Thermo Fisher Scientific Inc., Waltham, MA, USA; SSP Combi trays, Olerup SSP AB, Stockholm, Sweden) under ASHI requirements [8]. Maximumlikelihood (ML) frequencies for alleles and four-locus haplotypes were estimated using an Expectation-Maximization (EM) algorithm provided by the computer program Arlequin ver. 3.5 [9]. We chose the ML-EM algorithm to avoid under or overestimating the frequency of any allele and to obtain reliable allele frequency estimates regardless of the sample size used, the observed heterozygosity or the fact that loci are linked [9–11]. For a comprehensive review on the methods, such as sample collection, HLA typing and statistical analyses such as admixture estimations, please refer to [12] in this same issue. For the frequencies of HLA-A, -B, -DRB1 and -DQB1 and haplotypic data for the sample sets of the state of Zacatecas please refer to the Supplementary Information: Supplementary Tables 1–8. For data on Hardy-Weimberg equilibrium (HWE) please see Supplementary Information: Supplementary Table 9 of this work and Supplementary Information: Supplementary Table 3 in [12] in this same issue. We find that the most frequent haplotypes for the state (haplotypic frequency, H.F. > 1.0%, arbitrarily; Supplementary Table 5) include seven Native American MPA (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02;
Fig. 1. Geographic situation of Zacatecas and admixture proportions for the state of Zacatecas [Mexico Zacatecas, Zacatecas city (N = 84, AFND-ID: 3511), Mexico Zacatecas, Fresnillo (N = 103, AFND-ID: 3510) and Mexico Zacatecas Rural (N = 266, AFND-ID: 3577)]. Admixture proportions were estimated by a Maximum Likelihood method [18] using HLA-A, -B and -DRB1 frequencies as genetic estimators. Green refers to the proportion of European contribution, purple to Native American contribution and yellow depicts African contribution. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) 2
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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). There is an increase in the number of European MPA haplotypes in Fresnillo when compared with Zacatecas city and the rural areas, which can be explained by the slightly higher European contribution present in this population [55.46% vs 47.11% in Zacatecas city and 44.91% in the rural areas (Fig. 1)]. Admixture estimates (Fig. 1) revealed that the main genetic components in the state of Zacatecas are European (47.61 ± 1.85%, ranging from 44.91% in the rural areas to 55.46% in Fresnillo) and Native American (44.74 ± 1.12%, ranging from 41.39% in Fresnillo to 46.11% in Zacatecas city), while African genetic component was less apparent (7.65 ± 1.12%, going from 3.15% in Fresnillo to 9.55% in the rural areas). It is not surprising that both Zacatecas city and Fresnillo have similar ancestral components, as they follow very close demographic processes (mainly population growth and net emigration) [2]. A genome-wide single-nucleotide polymorphisms (SNPs) admixture estimation for the state of Zacatecas [13] found similar admixture estimates of European (45.7 ± 8.4%), Native American (51.1 ± 7.7%) and African (1.8 ± 2.3%) genetic components. These estimations differ from previous reports for the region in which European component was estimated to be 66.21 ± 4.49% and Native American estimated at 33.79 ± 4.49% using nine polymorphic blood groups [14] and from regional estimates using short-tandem repeats (STRs) [15] estimating components to be 59.8% European, 38.7% Native American and 1.5% African. In the former case, nevertheless, they only considered two biological parental populations (Europeans and Native Americans) for the estimations. The differences between the estimation of the African component could be due to differences in the admixture estimation methods (three loci of HLA vs whole genome SNP data) or differences in local genomic ancestry: there is an apparent increase in African ancestry in Latin American mixed ancestry populations that could be due to selection of such variants after the conquest and during the colonial period (discussed in [12] in this issue). The admixture proportions for Zacatecas City, Fresnillo and the rural areas of the state don’t show any major shifts to what we found at the state level (Fig. 1). In concordance with previous reports [16], we found a higher prevalence of Native American and African genetic components in the rural areas when compared to the cities. The admixture estimates and the presence of Native American, European and Asian haplotypes (Supplementary Table 5–8) can be explained by the aforementioned historical events that shaped the demographic traits of modern day Zacatecas. All data from our sample sets, both frequencies and individual genotypes, can be found at The Allele Frequency Net Database website (www.allelefrequencies.netwww. allelefrequencies.net) [17].
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Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.humimm.2019.01.007.
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Contents lists available at ScienceDirect
Human Immunology journal homepage: www.elsevier.com/locate/humimm
Genetic diversity of HLA system in three populations from Zacatecas, Mexico: Zacatecas city, Fresnillo and rural Zacatecas Diana Iraíz Hernández-Zaragozaa,b,1, Héctor Delgado-Aguirrec,1, Rodrigo Barqueraa,d, ,1, Carmen Adalid-Sáinzc,1, Stephen Claytond,1, Abraham Lona-Sáncheza, Liliana González-Medinaa, Hanna Pacheco-Ubaldoa, Alicia Bravo-Acevedoe, Néstor Escareño-Montielf, Javier Morán-Martínezg, Marisela del Rocío González-Martínezh, Yolanda Jaramillo-Rodríguezi, ⁎ ⁎ ⁎ Federico Juárez-de la Cruzf, Joaquín Zúñigaj,k, , Edmond Yunisl, , Carolina Bekker-Méndezm, , n,⁎ Julio Granados ⁎
a
Molecular Genetics Laboratory, Escuela Nacional de Antropología e Historia (ENAH), Mexico City, Mexico Immunogenetics Unit, Técnicas Genéticas Aplicadas a la Clínica (TGAC), Mexico City, Mexico c Laboratory of Histocompatibility, Unidad Médica de Alta Especialidad (UMAE) # 71, Instituto Mexicano del Seguro Social (IMSS), Torreón, Coahuila, Mexico d Department of Archaeogenetics, Max Planck Institute for the Science of Human History (MPI-SHH), Jena, Germany e Blood Bank, UMAE Hospital de Gineco Obstetricia No. 4 “Luis Castelazo Ayala”, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico f Department of Transplantation, Unidad Médica de Alta Especialidad (UMAE) # 71, Instituto Mexicano del Seguro Social (IMSS), Torreón, Coahuila, Mexico g Cellular Biology and Ultra Structure Department, Biomedical Research Center, Universidad Autónoma de Coahuila, Torreón, Coahuila, Mexico h Microbiology Department, Faculty of Medicine, Universidad Autónoma de Coahuila, Torreón, Coahuila, Mexico i Health Research Division, Unidad Médica de Alta Especialidad (UMAE) # 71, Instituto Mexicano del Seguro Social (IMSS), Torreón, Coahuila, Mexico j Laboratory of Immunobiology and Genetics, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico k Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico l Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA m Immunology and Infectology Research Unit, Infectology Hospital, Centro Médico Nacional “La Raza”, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico n Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ), Mexico City, Mexico b
ARTICLE INFO
ABSTRACT
Keywords: HLA Immunogenetics Population genetics Zacatecas Admixture
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 ± 1.85%) and Native American (44.74 ± 1.12%), while the African genetic component was less apparent (7.65 ± 1.12%). Our findings provide a starting point for the study of
Abbreviations: HLA, Human Leukocyte Antigen; MPA, Most-probable ancestry; LD, Linkage Disequilibrium ⁎ Corresponding authors at: Department of Archaeogenetics, Max Planck Institute for the Science of Human History. Kahlaische Strasse 10, 07745 Jena, Germany (R. Barquera). Laboratory of Immunobiology and Genetics, Research Division, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calz. De Tlalpan 4502, Bellisario Domínguez Sección XVI, 14080, Tlalpan, Mexico City, Mexico (J. Zúñiga). Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney St. #1234, Boston, MA 02215, USA (E. Yunis). Immunology and Infectology Research Unit, Infectology Hospital, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS), Calzada Vallejo y Jacarandas S/N Colonia La Raza, 02990 Mexico City, Mexico (C.B. Méndez). Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ), Vasco de Quiroga 15, Belisario Domínguez Sección XVI, 14080 Tlalpan, CDMX, Mexico (J. Granados). E-mail addresses: [email protected] (R. Barquera), [email protected] (J. Zúñiga), [email protected] (E. Yunis), [email protected] (C. Bekker-Méndez), [email protected] (J. Granados). URLs: http://www.shh.mpg.de/en (R. Barquera), http://www.iner.salud.gob.mx (J. Zúñiga), http://www.dana-farber.org (E. Yunis), http://www.cienciaimss.org/uim-en-inmunologia-e-infectologia/ (C. Bekker-Méndez), http://www.innsz.mx (J. Granados). 1 These authors contributed equally to the present work. https://doi.org/10.1016/j.humimm.2019.01.007 Received 10 December 2018; Received in revised form 22 January 2019; Accepted 23 January 2019 0198-8859/ © 2019 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.
Please cite this article as: Hernández-Zaragoza, D.I., Human Immunology, https://doi.org/10.1016/j.humimm.2019.01.007
Human Immunology xxx (xxxx) xxx–xxx
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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.
Zacatecas is located in the northern part of Mexico (Fig. 1), bordering with the states of Durango, Coahuila, Nuevo Leon, San Luis Potosi, Guanajuato, Jalisco and Nayarit. Of the 58 municipalities that make up the state by 2010 [1], 14% of the population lived in the municipality of Fresnillo, making it the most populated municipality in the state. This is the region from where the largest number of samples was collected. As in the rest of the country, the pattern of settlement in Zacatecas is characterized by a high dispersion across hundreds of locations paired with high demographic density in few urban centers [2]. In Zacatecas there are about 20 native languages, although only 0.3% of the population over 3 years of age speak an indigenous language, of which the first 5 places in percentage of speakers to 2015 are: Huichol (27.4%), Nahuatl (17.1%), southern Tepehuan (15%), Mazahua (5.56%) and Mixtec (4.46%) [1]. The territory that currently comprises the state of Zacatecas has been inhabited at least since the Classic period by the Chalchihuites, a social group that settled mainly in three large complexes: Suchil, Alta Vista and Guadiana (in Durango) who were engaged in agriculture and mineral extraction. This occupation continued until the Post Classic period, but there is no indication that it survived until the period of contact with Europeans [3,4]. Upon the arrival of the European conquerors, northern Mexico was known as the “Great Chichimeca” territory and was inhabited by groups of hunter-gatherers hostile to the Aztec empire. The settlement of mines, mostly for silver, was the main reason for Spanish companies to undertake the conquest and colonization of this territory, aided by the displacement of Purépecha and Otomí population mainly from 1548 onwards [4], and through the Colonial period also Tlaxcaltecans, Cholultecs and Tarascans [5]. Also during the Colonial period, the arrival of African enslaved individuals for working in the mines was constant, because like in the mines in Guanajuato and San Luis, there was not enough manpower for the extraction of metals, the indigenous population was in decline and did not represent profits for the encomenderos [6]. Throughout the first years of Independent Mexico, the situation in Zacatecas went into crisis, as many settlements were abandoned and most of the mines were closed. But with the coming to power of Porfirio Díaz, in 1877, Mexico undertook the process of modernization. Díaz ruled Mexico for more than three decades, pacified the country and achieved the development of its economy. At the end of the 19th century, as the enclave economy developed, Mexico needed cheap labor to work in the mines and build railroads. It was planned to recruit a large contingent of Chinese workers in the USA to work in Mexico. On December 14th, 1899, representatives of both governments officially signed the Treaty of Friendship, Commerce and Navigation between China and Mexico in Washington. In this way, the two countries formally established diplomatic relations [7] which allowed the entry of Chinese workers into the state as workforce for the construction of the railway lines. The twentieth century was defined by a population growth paired with rejuvenation along with an increase in the emigration to the US. By 1970, 5% of the national population lived in Zacatecas; however, the population growth of the state has been decreasing (with the natural growth being always below the national average since the 1970’s [2]) and, together with the lack of economic development opportunities and low economic growth that forced migrating not only to other states but also to the United States, it currently represents only 1.3% of the national population [1,2]. Forty one percent of the population lives in rural areas, while the rest lives in cities such as Fresnillo (the most populated one) and Zacatecas (the capital city) [1]. Only 0.3% of the population is considered Native American, one of the lowest proportions for the whole country [1].
For the present work, we analyzed HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) PCR-SSP based typings in 453 Mexicans from the state of Zacatecas [the state of Zacatecas data is composed by the following populations: Mexico Zacatecas, Zacatecas city (N = 84, Allele Frequencies Net Database Identifier (AFND-ID): 3511), Mexico Zacatecas, Fresnillo (N = 103, AFND-ID: 3510), Mexico Zacatecas Rural (N = 266, AFND-ID: 3577)]. Briefly, genomic DNA was extracted from peripheral blood using standardized procedures (DNA Isolation Kit for Mammalian Blood, Roche Diagnostics, Basel, Switzerland; automated DNA extraction with the MagNA Pure Compact System, Roche Molecular Systems, Pleasanton, CA, USA; inhouse validated salting out techniques), and DNA was adjusted to a final concentration of 80–120 ng/μL and stored at –20 °C until use. HLA genotyping was performed using commercially available PCR sequence-specific primers (PCR-SSP) kits (AB/DR/DQ SSP Unitray®, Life Technologies/ Thermo Fisher Scientific Inc., Waltham, MA, USA; SSP Combi trays, Olerup SSP AB, Stockholm, Sweden) under ASHI requirements [8]. Maximumlikelihood (ML) frequencies for alleles and four-locus haplotypes were estimated using an Expectation-Maximization (EM) algorithm provided by the computer program Arlequin ver. 3.5 [9]. We chose the ML-EM algorithm to avoid under or overestimating the frequency of any allele and to obtain reliable allele frequency estimates regardless of the sample size used, the observed heterozygosity or the fact that loci are linked [9–11]. For a comprehensive review on the methods, such as sample collection, HLA typing and statistical analyses such as admixture estimations, please refer to [12] in this same issue. For the frequencies of HLA-A, -B, -DRB1 and -DQB1 and haplotypic data for the sample sets of the state of Zacatecas please refer to the Supplementary Information: Supplementary Tables 1–8. For data on Hardy-Weimberg equilibrium (HWE) please see Supplementary Information: Supplementary Table 9 of this work and Supplementary Information: Supplementary Table 3 in [12] in this same issue. We find that the most frequent haplotypes for the state (haplotypic frequency, H.F. > 1.0%, arbitrarily; Supplementary Table 5) include seven Native American MPA (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02;
Fig. 1. Geographic situation of Zacatecas and admixture proportions for the state of Zacatecas [Mexico Zacatecas, Zacatecas city (N = 84, AFND-ID: 3511), Mexico Zacatecas, Fresnillo (N = 103, AFND-ID: 3510) and Mexico Zacatecas Rural (N = 266, AFND-ID: 3577)]. Admixture proportions were estimated by a Maximum Likelihood method [18] using HLA-A, -B and -DRB1 frequencies as genetic estimators. Green refers to the proportion of European contribution, purple to Native American contribution and yellow depicts African contribution. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) 2
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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). There is an increase in the number of European MPA haplotypes in Fresnillo when compared with Zacatecas city and the rural areas, which can be explained by the slightly higher European contribution present in this population [55.46% vs 47.11% in Zacatecas city and 44.91% in the rural areas (Fig. 1)]. Admixture estimates (Fig. 1) revealed that the main genetic components in the state of Zacatecas are European (47.61 ± 1.85%, ranging from 44.91% in the rural areas to 55.46% in Fresnillo) and Native American (44.74 ± 1.12%, ranging from 41.39% in Fresnillo to 46.11% in Zacatecas city), while African genetic component was less apparent (7.65 ± 1.12%, going from 3.15% in Fresnillo to 9.55% in the rural areas). It is not surprising that both Zacatecas city and Fresnillo have similar ancestral components, as they follow very close demographic processes (mainly population growth and net emigration) [2]. A genome-wide single-nucleotide polymorphisms (SNPs) admixture estimation for the state of Zacatecas [13] found similar admixture estimates of European (45.7 ± 8.4%), Native American (51.1 ± 7.7%) and African (1.8 ± 2.3%) genetic components. These estimations differ from previous reports for the region in which European component was estimated to be 66.21 ± 4.49% and Native American estimated at 33.79 ± 4.49% using nine polymorphic blood groups [14] and from regional estimates using short-tandem repeats (STRs) [15] estimating components to be 59.8% European, 38.7% Native American and 1.5% African. In the former case, nevertheless, they only considered two biological parental populations (Europeans and Native Americans) for the estimations. The differences between the estimation of the African component could be due to differences in the admixture estimation methods (three loci of HLA vs whole genome SNP data) or differences in local genomic ancestry: there is an apparent increase in African ancestry in Latin American mixed ancestry populations that could be due to selection of such variants after the conquest and during the colonial period (discussed in [12] in this issue). The admixture proportions for Zacatecas City, Fresnillo and the rural areas of the state don’t show any major shifts to what we found at the state level (Fig. 1). In concordance with previous reports [16], we found a higher prevalence of Native American and African genetic components in the rural areas when compared to the cities. The admixture estimates and the presence of Native American, European and Asian haplotypes (Supplementary Table 5–8) can be explained by the aforementioned historical events that shaped the demographic traits of modern day Zacatecas. All data from our sample sets, both frequencies and individual genotypes, can be found at The Allele Frequency Net Database website (www.allelefrequencies.netwww. allelefrequencies.net) [17].
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Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.humimm.2019.01.007.
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