RESUMO
The present study investigates the molecular basis of the G3m polymorphism expressed by the heavy constant domains of human immunoglobulins gamma 3 chains. By using a new protocol allowing the specific cloning of IGHG3 genes, a total of 51 full-length IGHG3 genomic sequences (about 2 kb) isolated from African, Siberian, West Asian and European population samples were sequenced. IGHG3 sequences were assigned precise G3m haplotypes on the basis of specific associations between G3m allotypes and IGHG3 RFLPs. Specific DNA substitutions involved in the expression of G3m(5), G3m(6), G3m(15), G3m(16), G3m(21), G3m(24) and G3m(28) allotypes were then deduced, elucidating almost completely the determination of the G3m polymorphism at the DNA level. The molecular evolution of G3m haplotypes was investigated by a maximum likelihood phylogeny of IGHG3 sequences. Sequence clusters are shown to be G3m haplotype-specific, corroborating the Gm molecular model deduced from serology, and showing that populations differentiation is much more recent than G3m haplotypes differentiation. The widely distributed G3m(5,10,11,13,14) haplotype is likely to be ancestral to the other G3m haplotypes presently found at high frequencies in different continental areas.
Assuntos
Alelos , Haplótipos/genética , Cadeias gama de Imunoglobulina/genética , Polimorfismo Genético/genética , Ásia Ocidental , Sequência de Bases , Etnicidade/genética , Europa (Continente) , Feminino , Frequência do Gene , Humanos , Masculino , Filogenia , Polimorfismo de Fragmento de Restrição , Senegal , SibériaRESUMO
We have identified two V lambda genes outside the major lambda locus on chromosome 22q11.2, and shown that they reside on chromosome 8q11.2. One gene (Orphée1), hybridizing strongly to the V lambda probes, was sequenced and found to belong to the V lambda 8 family; the other gene (Orphée2) only hybridized weakly. Orphée1 was present in all individuals tested (140) from three different populations, and was also found in gorillas. We envisage that these genes were generated by duplication and translocation of the V lambda 8a gene (and a V lambda pseudogene) from the major locus, and that this event occurred before the evolutionary divergence of humans and gorillas. As there is no other evidence for V lambda genes outside the major locus, it appears that the human lambda locus has undergone considerably less evolutionary shuffling than either the human light chain kappa locus or the heavy chain locus.
Assuntos
Cromossomos Humanos Par 8/genética , Genes de Imunoglobulinas/genética , Cadeias lambda de Imunoglobulina/genética , Família Multigênica , Sequência de Aminoácidos , Sequência de Bases , Cromossomos Humanos Par 22 , Sequência Conservada/imunologia , Humanos , Região Variável de Imunoglobulina/genética , Dados de Sequência Molecular , Translocação Genética/imunologiaRESUMO
Four of the five human IGHG genes (G1, GP, G2, and G4) display a hinge region consisting of a unique exon. In contrast, IGHG3 exhibits a different structure in which the hinge is constituted by four or, less frequently, three exons. We report here the nucleotide sequence of a new 2-exon hinge G3 gene found in a Mandenka individual from Eastern Senegal. A comparison of this sequence with that of 4-exon and 3-exon hinge G3 genes suggests that the 3-exon and 2-exon hinge forms arose independently by deletion events in a 4-exon hinge gene.
Assuntos
Éxons , Genes de Imunoglobulinas , Éxons Codificadores da Região de Dobradiça , Imunoglobulina G/genética , Cadeias Pesadas de Imunoglobulinas/genética , Polimorfismo Genético , Linfócitos B , Sequência de Bases , Linhagem Celular , Primers do DNA , Etnicidade/genética , Homozigoto , Humanos , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Mapeamento por Restrição , Senegal , Deleção de SequênciaRESUMO
This study presents restriction fragment length polymorphism (RFLP) and serological analyses of the immunoglobulin CH loci in a sample of 100 individuals from a Senegalese Mandenka population. The RFLP variability is mostly the result of large DNA insertions or deletions in the non-coding flanking regions of the IGHG genes, and to variable number of tandem repeat-like patterns within their 5'-switch sequences. However, part of the IGHG3 polymorphism also corresponds to a variable number of exons coding for the flexible hinge segment of the IgG3 antibody (the 4-exon and 3-exon forms, and a newly described 2-exon form). This diversity presents relevant associations with Gm haplotypes, suggesting that molecular rearrangements of the G3 hinge are related to the evolution of the Gm polymorphism. Non-significant correlation coefficients are found between Gm haplotypes and A2m alleles in the Mandenka, indicating that these loci may have reached equilibrium through recombination. The effect of recombination on linkage disequilibrium is more generally revealed, across the Ig CH genomic region, by a significant decrease of D' values with increasing physical distances between the loci on the chromosome.
Assuntos
Cromossomos Humanos Par 14/genética , Genes de Imunoglobulinas , Regiões Constantes de Imunoglobulina/genética , Alótipos Gm de Imunoglobulina/genética , Cadeias Pesadas de Imunoglobulinas/genética , Alelos , Evolução Molecular , Frequência do Gene/genética , Ligação Genética/genética , Haplótipos/genética , Humanos , Alótipos de Imunoglobulina/genética , Desequilíbrio de Ligação/genética , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , SenegalRESUMO
A sample of 162 Mandenkalu from Eastern Senegal has been typed for three HLA class I loci: HLA-A, -B and -C. The Mandenka population presents a very high genetic variability with 15 alleles for locus A, 24 alleles for locus B, and at least 8 alleles for locus C. The calculated heterozygosities for the three loci A, B, and C are respectively 0.884, 0.944 and 0.829. The Mandenkalu allelic frequencies are close to that found in other sub-Saharan populations. They show, however, some peculiarities like the occurrence of the Bw 56 allele and the high frequencies of both B5 and B35.
Assuntos
Genes MHC Classe I/genética , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Polimorfismo Genético/genética , Alelos , Distribuição de Qui-Quadrado , Heterozigoto , Humanos , Fenótipo , Senegal/epidemiologiaRESUMO
We present the results of AG antigen typings of three Caucasoid population samples: Lebanese, Tunisians, and Finns. AG haplotype frequencies estimated by maximum-likelihood methods are compared with the frequencies observed in 13 world populations previously tested for AG specificities by computing a genetic distance matrix used in a multivariate analysis. A high degree of polymorphism characterizes the three samples, with 10 haplotypes detected in the Lebanese and 11 haplotypes detected in the Tunisians and Finns; high heterozygosity levels are also present in the three populations. The genetic distance analysis shows that the three populations possess a genetic structure intermediate between those observed in sub-Saharan Africans and in Caucasoids from the Near East and India. This tight correspondence between AG differentiation and geography is confirmed by a highly significant correlation coefficient found between genetic and geographic distances computed worldwide, suggesting that an isolation by distance model of evolution applies to the AG system. The Ewens-Watterson test for selective neutrality on all world populations tested for AG specificities also supports the hypothesis that the AG system behaves like a neutral polymorphism. Overall, the AG differentiation pattern appears to be close to the patterns observed for other serological polymorphisms, such as RH, GM, and HLA, whose evolutionary mechanisms are also discussed.