Six novel HLA-B, -DRB1, and -DQB1 alleles identified in Brazilian individuals.

The novel HLA alleles B*40:331, B*40:343, B*42:24, DRB1*01:74, DQB1*03:243, and DQB1*03:02:20 were identified in Brazilian individuals.

High-resolution HLA allele and haplotype frequencies in majority and minority populations of Costa Rica and Nicaragua: Differential admixture proportions in neighboring countries.

The HLA system shows the most extensive polymorphism in the human genome. Allelic and haplotypic frequencies of HLA genes vary dramatically across human populations. Due to a complex history of migration, populations in Latin America show a broad variety of admixture proportions, usually varying not only between countries, but also within countries. Knowledge of HLA allele and haplotype frequencies is essential for medical fields such as transplantation, but also serves as a means to assess genetic diversity and ancestry in human populations. Here, we have determined high-resolution HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a sample of 713 healthy subjects from three Mestizo populations, one population of African descent, and Amerindians of five different groups from Costa Rica and Nicaragua and compared their profiles to a large set of indigenous populations from Iberia, Sub-Saharan Africa, and the Americas. Our results show a great degree of allelic and haplotypic diversity within and across these populations, with most extended haplotypes being private. Mestizo populations show alleles and haplotypes of putative European, Amerindian, and Sub-Saharan African origin, albeit with differential proportions. Despite some degree of gene flow, Amerindians and Afro-descendants show great similarity to other Amerindian and West African populations, respectively. This is the first comprehensive study reporting high-resolution HLA diversity in Central America, and its results will shed light into the genetic history of this region while also supporting the development of medical programs for organ and stem cell transplantation.

HFE gene polymorphism defined by sequence-based typing of the Brazilian population and a standardized nomenclature for HFE allele sequences.

The HFE molecule controls iron uptake from gut, and defects in the molecule have been associated with iron overload, particularly in hereditary hemochromatosis. The HFE gene including both coding and boundary intronic regions were sequenced in 304 Brazilian individuals, encompassing healthy individuals and patients exhibiting hereditary or acquired iron overload. Six sites of variation were detected: (1) H63D C>G in exon 2, (2) IVS2 (+4) T>C in intron 2, (3) a C>G transversion in intron 3, (4) C282Y G>A in exon 4, (5) IVS4 (-44) T>C in intron 4, and (6) a new guanine deletion (G>del) in intron 5, which were used for haplotype inference. Nine HFE alleles were detected and six of these were officially named on the basis of the HLA Nomenclature, defined by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System, and published via the IPD-IMGT/HLA website. Four alleles, HFE*001, *002, *003, and *004 exhibited variation within their exon sequences.

A novel HLA-A allele, A*74:23, identified in an individual from Costa Rica.

The new HLA-A*74:23 allele differs from the closest allele A*74:01 by a nucleotide change in exon 3 at codon 97.

Disaster triage after the Haitian earthquake.

In the aftermath of the devastating Haitian earthquake, we became the primary relief service for a large group of severely injured earthquake victims. Finding ourselves virtually isolated with extremely limited facilities and a group of critically injured patients whose needs vastly outstripped the available resources we employed a disaster triage system to organize their clinical care. This report describes the specific injury profile of this group of patients, their clinical course, and the management philosophy that we employed. It provides useful lessons for similar situations in the future.

High-resolution molecular characterization of the HLA class I and class II in the Tarahumara Amerindian population.

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 linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes.

KIR gene in ethnic and Mestizo populations from Mexico.

Killer cell immunoglobulin-like receptors are characterized by their great diversity of genes and alleles. Population studies have identified the presence of a broad variety of genotypes. In Mexico, there are diverse ethnic groups representing 9% of the total population and the rest is composed of Mestizos with a more varied biology. For the purpose of this study, genotyping was performed in Mestizos, in Mexico City inhabitants, and in three ethnic groups. The frequencies of genes KIR2DL2, 2DL5, 2DS1-3, 2DS5, and 3DS1 showed a greater variability in the groups studied. A total of 12 different genotypes were identified, the higher number for the Mestizos and the lower number for the Tarahumaras. Genotype 1 was found at a greater frequency in all the groups, except for the Tarahumaras, in which genotype 4 was more frequent. The frequency of genotypes 4 and 8 in Mexicans was higher than that for other populations analyzed. By subtyping of KIR3DL1, 3DL2, 2DL1, and 2DL3, two B haplotypes were identified in families; both were absent in Caucasian families. Our results indicated a greater diversity of genes in the Mestizos group than in the ethnic groups.

HLA class I diversity in Kolla Amerindians.

Human leukocyte antigen (HLA) class I polymorphism was studied within a population of 70 unrelated Kolla Amerindians from the far northwest of Argentina close to the Bolivian border. The results indicate that the HLA-A, -B, and -C alleles typical of other Amerindian populations also predominate in the Kolla. These alleles belong to the following allele groups: HLA-A*02, *68, *31, *24, HLA-B*35, *15, *51, *39, *40, *48, and Cw*01, *03, *04, *07, *08, and *15. For the HLA-A locus, heterogeneity was seen for HLA-A*02 with A*0201, *0211, and *0222; and for A*68 with *68012 and *6817, the latter being a novel allele identified in this population. Analysis of HLA-B identified heterogeneity for all Amerindian allele groups except HLA-B*48, including the identification of the novel B*5113 allele. For HLA-C heterogeneity was identified within the Cw*07, *04, and *08 groups with Cw*0701/06, *0702, *04011, *0404, *0803, and *0809 identified. The most frequent "probable" haplotype found in this population was B*3505-Cw*04011. This study supports previous studies, which demonstrate increased diversity at HLA-B compared with HLA-A and -C. The polymorphism identified within the Kolla HLA-A, -B, and -C alleles supports the hypothesis that HLA evolution is subject to positive selection for diversity within the peptide binding site.

Characterization of the HLA class I genotypes of a Venezuelan Amerindian group by molecular methods.

We have characterized the HLA class I genotypes of the Yucpa, a tribe of Venezuelan Amerindians, using molecular methods. The study was carried out on DNA extracted from unrelated individuals using low resolution ARMS-SSP typing with sequence-specific primers, high resolution typing using reference strand conformation analysis (RSCA), and for some samples sequence-based typing (SBT). The following class I alleles were found to be present in this tribe: for the HLA-A locus A*0204, A*0212, A*0213, A*2402, A*3101 and A*6801; for the B locus B*1522, B*3512, B*3905, B*3909, B*4004 and B*52012, and for C locus Cw*0102, Cw*0302/ 4, Cw*0401, Cw*0702 and Cw*1503. This is the first time these alleles have been described in this group, although all of them have previously been reported as being present in other Amerindian tribes. The study confirmed the high frequency of HLA-B39 which was previously observed in serological analysis of this tribe, and indicated that two different B*39 alleles were present in this population. The identification of the class I alleles by molecular methods for this ethnic group confirms the restricted polymorphism of the MHC molecules previously obtained by serology and has allowed a more accurate definition of the different alleles present in this population.