NGS-based typings for 7 HLA loci in two populations from Barra Mansa, RJ, Brazil.

We investigated HLA class I (HLA-A, -B, and -C) and class II (HLA-DRB1, -DQB1, -DPA1, and -DPB1) alleles by NGS-based typing among 478 Brazilian individuals from two populations in the Barra Mansa city based on their self-declared skin color (Caucasian, N = 405, AFND-ID: 3729; Black, N = 73, AFND-ID: 3731) to calculate allelic and haplotypic frequencies, plus linkage disequilibrium. No locus deviated from Hardy-Weinberg equilibrium. Both populations shared the most frequent allele on HLA-A, -C, -DPA1, and -DPB1. Genotype and frequency data are available in the Allele Frequencies Net Database.

NGS-based typings for 7 HLA loci in three populations from Rio de Janeiro, RJ, Brazil.

We investigated HLA class I (HLA-A, -B, and -C) and class II (HLA-DRB1, -DQB1, -DPA1, and -DPB1) alleles by NGS-based typing among 759 Brazilian individuals from three populations in the Rio de Janeiro city based on their self-declared skin color (Caucasian, N = 521, AFND-ID: 3730; Parda, N = 170, AFND-ID: 3728; Black, N = 68, AFND-ID: 3727) to calculate allelic and haplotypic frequencies, plus linkage disequilibrium. Only HLA-DRB1 locus deviated from Hardy-Weinberg equilibrium (in Caucasian and Black populations). The three populations shared the most frequent allele on HLA-A, -C, -DRB1, -DPA1, and -DPB1. Genotype and frequency data are available in the Allele Frequencies Net Database.

An NGS-based HLA haplotype analysis and population comparison between two cities in Rio de Janeiro, Brazil.

HLA genes can exhibit extensive variations in frequency, especially in highly admixed populations, such as that of Brazil. In this study, we demonstrated NGS-based HLA typing in our laboratory using an Illumina HiSeq 2500 sequencing platform and downstream analysis. We herein describe and compare the allele and haplotype frequencies of the populations in Barra Mansa (BM) and Rio de Janeiro (RJ), using the acquired genetic data. Sequences encompassing 7 HLA loci (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, HLA-DPA1, and HLA-DPB1) were amplified from a total of 1435 bone marrow samples donated by volunteers recruited in BM (37.56%) and RJ (62.44%) using polymerase chain reactions, and were sequenced using five distinct HiSeq 2500 runs. Alleles were analyzed to generate 2-locus haplotypes and extended haplotypes encompassing more than two loci. The most frequent haplotype was A*01:01:01~C*07:01:01~B*08:01:01~DRB1*03:01:01~DQB1*02:01:01~DPA1*01:03:01~DPB1*04:01:01 in both populations. The populations of BM and RJ exhibited a significant difference in genetic composition (P = .03) but not in genetic variance (P = .45). However, some groups of subjects, classified based on self-declared ethnicity, particularly Branca and Preta, displayed significant genetic variance (P < .05). In conclusion, these genetic data indicate no differences in HLA loci between the populations of these two cities, but were informative with respect to variations in ancestry composition.

HLA class II genotyping of admixed Brazilian patients with type 1 diabetes according to self-reported color/race in a nationwide study.

The HLA region is responsible for almost 50% of the genetic risk of type 1 diabetes (T1D). However, haplotypes and their effects on risk or protection vary among different ethnic groups, mainly in an admixed population. We aimed to evaluate the HLA class II genetic profile of Brazilian individuals with T1D and its relationship with self-reported color/race. This was a nationwide multicenter study conducted in 10 Brazilian cities. We included 1,019 T1D individuals and 5,116 controls matched for the region of birth and self-reported color/race. Control participants belonged to the bone marrow transplant donor registry of Brazil (REDOME). HLA-class II alleles (DRB1, DQA1, and DQB1) were genotyped using the SSO and NGS methods. The most frequent risk and protection haplotypes were HLA~DRB1*03:01~DQA1*05:01 g~DQB1*02:01 (OR 5.8, p < 0.00001) and HLA~DRB1*07:01~DQA1*02:01~DQB1*02:02 (OR 0.54, p < 0.0001), respectively, regardless of self-reported color/race. Haplotypes HLA~DRB1*03:01~DQA1*05:01 g~DQB1*02:01 and HLA~DRB1*04:02~DQA1*03:01 g~DQB1*03:02 were more prevalent in the self-reported White group than in the Black group (p = 0.04 and p = 0.02, respectively). The frequency of haplotype HLA~DRB1*09:01~DQA1*03:01 g~DQB1*02:02 was higher in individuals self-reported as Black than White (p = <0.00001). No difference between the Brazilian geographical regions was found. Individuals with T1D presented differences in frequencies of haplotypes within self-reported color/race, but the more prevalent haplotypes, regardless of self-reported color/race, were the ones described previously in Europeans. We hypothesize that, in the T1D population of Brazil, although highly admixed, the disease risk alleles come mostly from Europeans as a result of centuries of colonization and migration.