High-resolution molecular characterization of the HLA class I and class II in the Tarahumara Amerindian population J. E. Garcı ´a-Ortiz 1,2 , L. Sandoval-Ramı´rez 2,3 , H. Rangel-Villalobos 3,4 , H. Maldonado-Torres 5 , S. Cox 5 , C. A. Garcı ´a-Sepu ´ lveda 5 , L. E. Figuera 2,3 , S. G. E. Marsh 5 , A. M. Little 5 , J. A. Madrigal 5 , J. Moscoso 6 , A. Arnaiz-Villena 6 & J. R. Argu ¨ ello 1 1 Departamento de Inmunobiologı ´a Molecular, Centro de Investigacio ´ n Biome ´ dica, Facultad de Medicina, Universidad Auto ´ noma de Coahuila, 27000 Torreo ´ n, Me ´ xico 2 Divisio ´n de Gene ´ tica, Centro de Investigacio ´ n Biome ´ dica de Occidente, CMNO-IMSS, 44340 Guadalajara, Me ´ xico 3 Doctorado en Gene ´ tica Humana, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, Me ´ xico 4 Laboratorio de Gene ´ tica Molecular, Centro Universitario de la Cie ´ nega, Universidad de Guadalajara (CUCI-UdeG), Ocotla ´ n, Jalisco, Me ´ xico 5 The Anthony Nolan Research Institute, and Royal Free & UCL School of Medicine, Royal Free Campus, Hampstead, London, UK 6 Departamento de Inmunologı ´a y Biologı ´a Molecular, Hospital 12 de Octubre, Universidad Complutense, 28040 Madrid, Espan ˜a Key words Amerindian; HLA alleles; MHC; RSCA; Tarahumara Correspondence J. Rafael Argu ¨ello, MD, PhD Departamento de Inmunobiologı ´a Molecular Centro de Investigacio ´ n Biome ´ dica Facultad de Medicina Universidad Auto ´ noma de Coahuila Gregorio A. Garcı ´a 198 Sur, CP 27000 Torreo ´ n, Coahuila Me ´ xico Tel: þ52 871 7226470 Fax: þ52 871 7226470 e-mail: rarguello@mail.uadec.mx Received 9 December 2005; revised 9 February 2006; re-revised 28 March 2006 and 11 May 2006; accepted 13 May 2006 doi: 10.1111/j.1399-0039.2006.00636.x Abstract We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and lin- guistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes. Introduction The most polymorphic genetic system in humans is the MHC, located on 6p21.31; 40% of 224 loci are related to immune function (1). Recent advances in molecular biol- ogy have revealed the extent of polymorphism at these loci (2). Amerindian populations are characterized by restricted levels of polymorphism both in HLA class I and class II alleles, but several studies have found new variants, particularly at the HLA-B locus, many of them the result of gene conversion or interallelic recombination events (3, 4). To extend and refine the analysis of HLA alleles in relation to population movement and develop- ment through time, we have carried out the first high- resolution HLA profile (HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1) of a Mexican Amerindian group: the Tarahumaras. They have an estimated population of approximately 121,835 inhabitants (75,534 being monolin- gual and older than 5 years of age) organized in very small communities (two to five families) distributed in the moun- tains and canyons of the Sierra Madre Occidental in Northwest of Mexico (Figure 1). Tarahumaras call them- selves Raramuri (‘the fleet-footed ones’). They are acknowledged to be among the few tribes in North America that have preserved their traditional lifestyle almost unmodified by three and a half centuries of contact with Caucasian and Mexican mestizo populations (5), maybe due to cultural and geographic reasons. Their Tissue Antigens ISSN 0001-2815 ß 2006 The Authors Journal compilation 68 (135–146) ß 2006 Blackwell Munksgaard 135