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

ABSTRACT: 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.

• Autores: Bedoya Berrío, Gabriel de Jesús; Ruíz Linares, Andrés; Hernández Zaragoza, Diana Iraíz; Bravo Acevedo, Alicia; Arrieta Bolaños, Esteban; Clayton, Stephen; Acuña Alonzo, Víctor; Martínez Álvarez, Julio César; López Gil, Concepción; Adalid Sáinz, Carmen; Vega Martínez, María Del Rosario; Escobedo Ruíz, Araceli; Juárez Cortés, Eva Dolores; Immel, Alexander; Pacheco Ubaldo, Hanna; González Medina, Liliana; Lona Sánchez, Abraham; Lara Riegos, Julio; Sánchez Fernández, María Guadalupe de Jesús; Díaz López, Rosario; Guizar López, Gregorio Ulises; Medina Escobedo, Carolina Elizabeth; Arrazola García, María Araceli; Montiel Hernández, Gustavo Daniel; Ramos de la Cruz, Flor del Rocío; Hernández Hernández, Ofelia; Juárez Nicolás, Francisco; Pantoja Torres, Jorge Arturo; Rodríguez Munguía, Tirzo Jesús; Juárez Barreto, Vicencio; Delgado Aguirre, Héctor; Escutia González, Ariadna Berenice; Goné Vázquez, Isis; Benítez Arvizu, Gamaliel; Arellano Prado, Francia Paulina; García Arias, Víctor Eduardo; Rodríguez López, Marla Estefanía; Méndez Mani, Patricia; García Álvarez, Raquel; González Martínez, Marisela Del Rocío; Méndez Mani, Patricia; García Álvarez, Raquel; Vázquez Castillo, Tannya Verónica; Uribe Duarte, María Guadalupe; Ruíz Corral, María de Jesús; Ortega Yáñez, Andrea; Bernal Felipe, Natalia; Gómez Navarro, Benjamín; Arriaga Perea, Agustín Jericó; Martínez Bezies, Virginia; Macías Medrano, Rosa María; Aguilar Campos, Jesús Abraham; Solís Martínez, Raúl; Serrano Osuna, Ricardo; Sandoval Sandoval, Mario J.; Jaramillo Rodríguez, Yolanda; Salgado Adame, Antonio; Juárez de la Cruz, Federico; Novelo Garza, Bárbara; Pavón Vargas, María de Los Ángeles; Salgado Galicia, Norma; Bortolini, Maria Cátira; Gallo, Carla; Rothhammer, Francisco; González José, Rolando; Barquera, Rodrigo; Canizales Quinteros, Samuel; Romero Hidalgo, Sandra; Krause, Johannes; Zúñiga, Joaquín; Yunis, Edmond J; Bekker Méndez, Carolina; Granados, Julio
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/41103
• Acceso en línea: https://hdl.handle.net/10495/41103
• Palabra clave: Alleles; Alelos; DNA; ADN; Gene Frequency; Frecuencia de los Genes; Genetics, Population; Genética de Población; Genome, Human; Genoma Humano; HLA Antigens; Antígenos HLA; Haplotypes; Haplotipos; Linkage Disequilibrium; Desequilibrio de Ligamiento; Major Histocompatibility Complex; Complejo Mayor de Histocompatibilidad; Polymorphism, Single Nucleotide; Polimorfismo de Nucleótido Simple; https://id.nlm.nih.gov/mesh/D000483; https://id.nlm.nih.gov/mesh/D004247; https://id.nlm.nih.gov/mesh/D005787; https://id.nlm.nih.gov/mesh/D005828; https://id.nlm.nih.gov/mesh/D015894; https://id.nlm.nih.gov/mesh/D006680; https://id.nlm.nih.gov/mesh/D006239; https://id.nlm.nih.gov/mesh/D015810; https://id.nlm.nih.gov/mesh/D008285; https://id.nlm.nih.gov/mesh/D020641
• Rights: openAccess
• License: http://creativecommons.org/licenses/by-nc-nd/2.5/co/