RESUMEN
Supertypes are groups of human leukocyte antigen (HLA) alleles which bind overlapping sets of peptides due to sharing specific residues at the anchor positions-the B and F pockets-of the peptide-binding region (PBR). HLA alleles within the same supertype are expected to be functionally similar, while those from different supertypes are expected to be functionally distinct, presenting different sets of peptides. In this study, we applied the supertype classification to the HLA-A and HLA-B data of 55 worldwide populations in order to investigate the effect of natural selection on supertype rather than allelic variation at these loci. We compared the nucleotide diversity of the B and F pockets with that of the other PBR regions through a resampling procedure and compared the patterns of within-population heterozygosity (He) and between-population differentiation (G ST) observed when using the supertype definition to those estimated when using randomized groups of alleles. At HLA-A, low levels of variation are observed at B and F pockets and randomized He and G ST do not differ from the observed data. By contrast, HLA-B concentrates most of the differences between supertypes, the B pocket showing a particularly high level of variation. Moreover, at HLA-B, the reassignment of alleles into random groups does not reproduce the patterns of population differentiation observed with supertypes. We thus conclude that differently from HLA-A, for which supertype and allelic variation show similar patterns of nucleotide diversity within and between populations, HLA-B has likely evolved through specific adaptations of its B pocket to local pathogens.
Asunto(s)
Evolución Biológica , Genética de Población , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Polimorfismo Genético/genética , Selección Genética/genética , Simulación por Computador , Bases de Datos Factuales , Antígenos HLA-A/clasificación , Antígenos HLA-A/inmunología , Antígenos HLA-B/clasificación , Antígenos HLA-B/inmunología , Prueba de Histocompatibilidad , Humanos , Epítopos Inmunodominantes , Agencias InternacionalesRESUMEN
The new allele might have arisen from HLA-A*66:01 through a point mutation at codon 182.1 (ACGâGCG) resulting in a non-conservative change from threonine to alanine.
Asunto(s)
Alelos , Antígenos HLA-A/clasificación , Antígenos HLA-A/genética , Mutación Puntual , Donantes de Tejidos , Secuencia de Bases , Brasil , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
HLA-A and HLA-B genes were typed by DNA sequencing in a mestizo population from Guadalajara, Jalisco, Mexico. Thirty-seven HLA-A and 51 HLA-B alleles were observed in 103 samples. The common typical Amerindian alleles (>5%) and haplotypes (>or=2.0%) found were A*02010101, *24020101, *310102, B*350101, and *4002, and A*310102-B*4002, A*240201-B*350101, and the typical European alleles were A*010101, *29010101, B*1402, B*180101, and A*020101-B*1402, A*020101-B*510101, and A*3002-B*180101. This reflects the blending of the two main parental populations of mestizos: Amerindian and Iberian. Mexicans were found to be relatively closer to the Portuguese than to Spaniards. This proximity may indicate a larger Portuguese influence in Mexicans than previously considered. Present data contribute to the understanding of the genetic structure in Mexico.
Asunto(s)
Frecuencia de los Genes , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Genética de Población , Antígenos HLA-A/clasificación , Antígenos HLA-B/clasificación , Haplotipos , Prueba de Histocompatibilidad , Humanos , México , Filogenia , Portugal , Análisis de Secuencia , EspañaRESUMEN
The variation and frequency of HLA-A genotypes were established by PCR-SSOP typing in diverse geographically distributed populations: Brazilian, Colombian Kogui, Cuban, Mexican, Omani, Singapore Chinese, and South African Zulu. HLA-A allelic families with only one allele were identified for HLA-A*01, -A*23, -A*25, -A*31, -A*32, -A*36, -A*43, -A*69, -A*80; and with two alleles for HLA-A*03, -A*11, -A*26, -A*29, -A*33, -A*34, and -A*66. Greater variation was detected for HLA-A*02, -A*24, and -A*68 allele families. Colombian Kogui and Mexican Seris showed the least diversity with respect to HLA-A alleles, albeit with small numbers tested, with only four and five HLA-A alleles identified, respectively. It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation.
Asunto(s)
Genética de Población , Antígenos HLA-A/clasificación , Antígenos HLA-A/genética , Prueba de Histocompatibilidad/métodos , Reacción en Cadena de la Polimerasa/métodos , África , Alelos , Brasil , China , Genotipo , Humanos , Indígenas Norteamericanos , México , OmánRESUMEN
HLA-A, -B and -C genes were analysed in the population living in the metropolitan region of Curitiba, the main city of Parana State, southern Brazil, to provide data for studies and applications in HLA-related fields, and to contribute to the understanding of human microevolution. Heterozygosity is high (95-99%) for all three loci. Frequencies for most alleles and haplotypes of sub-Saharan African and of European ancestry presented a clear gradient between the White, Mulatto and Black subpopulations. Among Whites, the four most common haplotypes were A*01-Cw*07-B*0801, A*02-Cw*07-B*07, A*11-Cw*0401-B*35 and A*03-Cw*0401-B*35. Their frequencies ranged from 5.6% to 3.0%. In the Mulatto sub-population, six haplotypes presented very similar frequencies, close to 2.0-2.4%: A*02-Cw*03-B*15, A*02-Cw*0401-B*35, A*02-Cw*07-B*07, A*03-Cw*0401-B*35, A*30-Cw*17-B*4201, A*68-Cw*03-B*15. Haplotype A*30-Cw*17-B*4201 was found to be very common (6.6%) in the Black sub-population. Admixture estimate revealed the relative contributions of Europeans, sub-Saharan Africans and Amerindians to this populations which were, respectively, 94%, 3% and 3% for the White sub-population, 57%, 39% and 4% for the Mulatto sub-population, and 25%, 74% and 1% for the Black sub-population.
Asunto(s)
Etnicidad , Antígenos HLA/genética , Polimorfismo Genético , Alelos , Brasil , Frecuencia de los Genes , Antígenos HLA/clasificación , Antígenos HLA-A/clasificación , Antígenos HLA-A/genética , Antígenos HLA-B/clasificación , Antígenos HLA-B/genética , Antígenos HLA-C/clasificación , Antígenos HLA-C/genética , Heterocigoto , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa/métodosRESUMEN
Serological HLA types (A, B, C, DR and DQ loci) were studied in five different Indian tribes (Cubeo, Tucano, Coreguaje, Embera and Noanama) belonging to two distinct linguistic families. For all the MHC loci, the range of variation among the five tribes was enormous. Two tribes, Cubeo and Tucano, showed a wide spectrum of antigenic specificities which seemed to be due to admixture from non-tribal groups, while in the other three tribes the polymorphisms of various HLA loci showed restricted distributions. The gene frequency data, when converted to a kinship matrix and a two-dimensional eigenvector plot, indicated that members of the same linguistic family tend to have greater genetic affinity.