RESUMO
The haplotypes of the alpha-globin gene cluster were determined for 99 Indians from the Brazilian Amazon region who belong to 5 tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Three predominant haplotypes were identified: Ia (present in 38.9% of chromosomes), IIIa (25.8%), and IIe (22.1%). The only alpha-globin gene rearrangement detected was alpha alpha alpha 3.7 I gene triplication associated with haplotype IIIa, found in high frequencies (5.6% and 10.6%) in two tribes and absent in the others. alpha-Globin gene deletions that cause alpha-thalassemia were not seen, supporting the argument that malaria was absent in these populations until recently. The heterogeneous distribution of alpha-globin gene haplotypes and rearrangements among the different tribes differs markedly from the homogeneous distribution of beta-globin gene cluster haplotypes and reflects the action of various genetic mechanisms (genetic drift, founder effect, consanguinity) on small isolated population groups with a complicated history of divergence-fusion events. The alpha-globin gene haplotype distribution has some similarities to distributions observed in Southeast Asian and Pacific Island populations, indicating that these populations have considerable genetic affinities. However, the absence of several features of the alpha-globin gene cluster that are consistently present among the Pacific Islanders suggests that the similarity of haplotypes between Brazilian Indians and people from Polynesia, Micronesia, and Melanesia is more likely to result of ancient common ancestry rather than the consequence of recent direct genetic contribution through immigration.
Assuntos
Frequência do Gene , Globinas/genética , Haplótipos/genética , Indígenas Sul-Americanos/genética , Alelos , Sequência de Bases , Brasil , Rearranjo Gênico , Humanos , Dados de Sequência MolecularRESUMO
We have studied seven Jamaican Negro families in whom the genes for alpha thalassaemia and the sickle cell mutation (betas) were independently segregated. Using a combination of techniques we identified two alpha thalassaemia phenotypes which resemble the severe (alpha thalassaemia 1) and mild (alpha thalassaemia 2) determinants previously described in Orientals. This study has enabled us to clearly correlate the phenotype of alpha thalassaemia with the genotype in this population. Furthermore, since in each family alpha thalassaemia was present in association with the gene for the sickle cell mutation we have determined the proportion of Hb S in the peripheral blood of individuals with the alpha alpha/alpha alpha, -alpha/alpha alpha and -alpha/-alpha genotype who are also heterozygous for the betas mutation. Genetic analysis in these families shows that in each case subjects with the alpha thalassaemia 1 phenotype are homozygous for the alpha thalassaemia 2 defect (-alpha/-alpha). We have found no instances of the genotype --/alpha alpha in this population which may explain the rarity of the severe alpha thalassaemia syndromes in Jamaica. Restriction mapping data in the alpha thalassaemia 2 homozygotes from this population shows that the (-alpha/) haplotype results from a deletion of one of the linked pair of alpha globin genes and that this has probably arisen by an unequal crossover between non-homologous alpha genes.
Assuntos
População Negra , Hemoglobina Falciforme/análise , Talassemia/genética , Mapeamento Cromossômico , DNA/sangue , Feminino , Genótipo , Heterozigoto , Homozigoto , Humanos , Jamaica , Masculino , Linhagem , Fenótipo , Talassemia/sangueRESUMO
A prospective study of 2191 Negro infants in Jamaica showed that approximately 7% of them had detectable levels of Hb Bart's (gamma 4) in the neonatal period. The red cell indices, globin chain biosynthesis and restriction endonuclease mapping of DNA from these infants were used to determine the significance of Hb Bart's at birth. The results indicate that the genotypes alpha alpha/alpha alpha, -- alpha/alpha alpha and -- alpha/ -- alpha are associated with 0%, 0.1-2%, and greater than 2% Hb Bart's respectively. Although trace amounts of Hb Bart's may be associated with the genotype -- alpha/alpha alpha this is not always the case and therefore haemoglobin analysis in the neonatal period cannot be used to diagnose this genotype with any certainty.
Assuntos
População Negra , Talassemia/diagnóstico , DNA , Índices de Eritrócitos , Genótipo , Globinas/biossíntese , Hemoglobinas Anormais/análise , Humanos , Lactente , Recém-Nascido , Jamaica , Estudos Prospectivos , Talassemia/sangue , Talassemia/genéticaRESUMO
The different alpha thalassemia genotypes in American and Jamaican black populations have been defined by hematologic and globin-chain synthesis studies, alpha/beta globin messenger RNA ratios and restriction endonuclease mapping of DNA. The results indicate that the common form of alpha thalassemia in these populations is the deletion type of alpha-thalassemia 2 (- alpha/alpha alpha). The homozygous state (- alpha/alpha- alpha) is expressed at birth by the presence of more than 2--3% hemoglobin Bart's; in adult life it has the same phenotype as the heterozygous state for the deletion form of alpha-thalassemia 1 (--/alpha alpha). The heterozygous state is not always associated with detectable amounts of hemoglobin Bart's at birth or with recognizable hematologic changes in adults.
Assuntos
População Negra , Hemoglobinas Anormais , Talassemia/genética , Feminino , Genótipo , Hemoglobinas Anormais/genética , Humanos , Lactente , Recém-Nascido , Jamaica , Masculino , América do Norte , Linhagem , Fenótipo , Talassemia/epidemiologiaRESUMO
The structure, synthesis, genetic transmission, clinical associations and distribution of the elongated alpha-chain haemoglobin variants has been described. The data indicate that the most likely molecular basis for these common abnormal haemoglobins is a single base substitution in the alpha-chain termination codon. Because these variants are produced inefficiently they give rise to the clinical picture of alpha-thalassaemia. When these findings are taken together with recent work regarding the molecular basis for other forms of alpha-thalassaemia it is possible to build up a fairly complete picture of the molecular pathology of the alpha-thalassaemias.