RESUMO
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.
Assuntos
Genes MHC da Classe II , Genes MHC Classe I , Indígenas Norte-Americanos/genética , Filogenia , Etnicidade/genética , Geografia , Haplótipos , Análise Heteroduplex , Humanos , Idioma , México , Polimorfismo GenéticoRESUMO
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.
Assuntos
Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Indígenas Sul-Americanos/genética , Alelos , Argentina , Feminino , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Haplótipos/imunologia , Teste de Histocompatibilidade/métodos , Teste de Histocompatibilidade/normas , Humanos , Masculino , Conformação de Ácido Nucleico , Sondas de Oligonucleotídeos/genética , Reação em Cadeia da Polimerase/métodos , Polimorfismo Genético/imunologia , Valores de Referência , Análise de Sequência de DNARESUMO
Two novel HLA-A and three novel HLA-B alleles were identified within a group of Afro-Caribbean individuals who were recruited as potential donors for the Anthony Nolan Bone Marrow Trust Register. HLA typing was performed on DNA extracted from peripheral blood mononuclear cells using sequence-specific oligonucleotide (SSO) probes for HLA-A and -B loci. Eight individuals analysed exhibited hybridisation patterns for which a type could not be assigned. DNA from these individuals was further typed by two methodologies: direct sequencing of PCR products and reference strand conformation analysis (RSCA). The direct sequencing results allowed the identification of new alleles but did not allow confirmation of the cis/trans orientation of the new sequence motifs identified. RSCA analysis confirmed the results obtained by SSO and direct sequencing and in addition confirmed the cis/trans orientation of the new sequences. One individual possesses a new A*30 allele--A*3008 and two individuals possess an identical new A*74 allele--A*7404. The three novel HLA-B alleles were identified in three individuals: B*0812, B*1554 and B*4503 respectively. For the remaining two samples, A*2612 was identified. At present Caucasoid individuals, and therefore Caucasoid phenotypes, are predominantly represented on the various different volunteer bone marrow donor registries. The examples presented here highlight the potential for identification of further polymorphisms within the HLA system as more individuals from the much-needed ethnic minorities are recruited onto bone marrow donor registers.
Assuntos
Transplante de Medula Óssea/imunologia , Variação Genética/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Doadores de Tecidos , Alelos , População Negra/genética , Marcadores Genéticos/imunologia , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Índias Ocidentais/etnologiaRESUMO
Analysis of HLA polymorphism of the indigenous populations of Central and South America has identified many alleles not seen previously in other populations. We have described a novel allele, B*5113, previously in a Kolla Amerindian individual from North-West Argentina. Here we present a second novel allele from this population: A*6817, which differs from its closest neighbour A*68012 by a single substitution at nucleotide 419. This substitution of adenosine 419 A*68012 for thymidine in A*6817 results in a novel amino acid change (aspartate to valine) at residue 116.
Assuntos
Antígenos HLA-A/genética , Indígenas Sul-Americanos/genética , Polimorfismo de Nucleotídeo Único , Argentina , Humanos , Dados de Sequência MolecularRESUMO
A novel HLA-B51 allele, B*5113, was identified in a Kolla Amerindian individual from North-West Argentina. HLA-B*5113 differs from B*51011 by two nucleotide substitutions, one synonymous, the other nonsynonymous. The resulting amino acid difference at residue 116 in the HLA-B molecule's peptide binding site is likely to affect the nature of the peptides which bind to this molecule. The finding of this novel allele supports previous findings of increased diversity at HLA-B in Amerindian groups.