Molecular variation at the HLA‐A, B, C, DRB1, DQA1, and DQB1 loci in full heritage American Indians in Arizona: private haplotypes and their evolution

Abstract

A sample of 492 full heritage, unrelated residents of the Gila River Indian Community (GRIC) of Arizona were characterized for their high resolution DNA alleles at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci. Only 5 allelic categories are found at HLA-A, 10 at HLA-B, 8 at HLA-C and HLA-DR, and 4 at DQA1 and DQB1. There is little evidence for population structure at the 6 loci. Two "private" alleles, B*5102 and B*4005, that are found nearly exclusively in American Indian populations in the desert southwest and northern Mexico, are likely new mutations after the first inhabitation of the area, the evolution of which are reflected in the contemporary distribution of their respective haplotypes. DRB1*1402 has the highest reported frequency of any specificity at the DRB1 locus, 0.7461, and serves as a sensitive probe for locating related east Asian populations. The haplotypes in this population also exhibit a highly restricted distribution and strong genetic disequilibria, which has important implications for matching solid organ and bone marrow allografts. It is shown that, when one considers HLA-A-B-DRB1 homozygotes as allograft donors for all full heritage members of the GRIC, 50% of the community would find a non-mismatched organ within the homozygotes for the 6 most common haplotypes. This raises questions about transplantation policy and whether, in the presence of high frequency private alleles and a restricted number of haplotypes, the full heritage American Indian community of the desert southwest should act as its own pool of donors for its affected members.

HLA Class I and Class II Conserved Extended Haplotypes and Their Fragments or Blocks in Mexicans: Implications for the Study of Genetic Diversity in Admixed Populations

“…Principal Components Analysis (PCA) for 38 populations with HLA-B data available was performed using the IBM SPSS Statistics 19 software ( IBM Corporation, Armonk, NY, USA ) to analyse the distribution of HLA-B alleles in human groups of the proposed ancestries, Figure 1 . PCA included population data of Ireland [20], NW of England [61], Germany [62], Austria [63]; Spain, Italy, United Kingdom [64], France [65], Gypsy from Andalucía (Spain; data collected by López-Nevot et al ) [14], Azores Terceira Island [66], Forro from São Tomé Island [67], Beti from Cameroon [68], Bandiagara from Mali, Lusaka from Zambia, Luo and Nandi from Kenia [69], Mandeka from Senegal [70], Guinea Bissau [71], Aleut from Bering Island (Russia) [72], center of Japan [73], a cord blood bank of Tzu Chi Foundation (Taiwan) [74], Han from southern China [60], north India [75], Kensiu from Malasya [76], Kinh from Vietnam [77], Tarahumara from northern Mexico [17], Native Americans from Gila River (USA) [78], Yu’pik from Alaska (USA) [79], Mixtec, Zapotec, and Mixe from Oaxaca (Mexico) [16], Seri from Sonora (Mexico) [80], Navajo from New Mexico (USA) [81], Uro from Titikaka Lake (Peru) [82], and Toba from Rosario (Argentina; data collected by Cintia Marcos et al ) [14]. Also, two admixed populations from Mexico were included: a “Mexican Mestizo” sample [83] and a sample from Guadalajara City, western Mexico [23].…”

HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased insulin secretion

“…In the Pima population rs9268852*A is highly concordant with HLA-DRB1*02. From a previous study of the highresolution HLA variation in full-heritage Pimans, it is known that the molecular allele is HLA-DRB1*1602 [7].…”

“…HLA-DR sample (n=613). This was a subset of the population sample that was typed for the HLA-DR locus either by serological or high-resolution DNA methods [6,7].…”

“…In prospective studies, obesity, insulin resistance and the acute insulin response (AIR) predicted the disease [3,4]. More than 2,000 Pima Indians have been characterised for HLA genotypes, which has led to the definition of new alleles at the HLA-B, HLA-C and DRB1 loci and descriptions of the distribution and population genetics of HLA variation in persons of full Pima heritage [5][6][7]. Recently, 100 K [8] and 1 M [9] single-nucleotide polymorphism (SNP) genomewide association studies have been conducted in this population.…”

Immunology in the Clinic Review Series; focus on host responses: T cell responses to herpes simplex viruses

“…In most ethnic groups, HLA‐A*0201 is one of the most abundant of the HLA‐A alleles: within the United States, 28% Caucasian, 20% Hispanic, 12% African Americans and 9% Asian‐Pacific Islanders possess the HLA‐A*0201 allele, with high frequencies also observed for some native American tribes [66–71]. Discovery of HLA A*0201‐restricted epitopes should, thus, benefit generation of a vaccine with high population coverage.…”