RESUMO
In a survey of the chromosomal background associated with the sickle cell gene in Guadeloupe, a French Caribbean island, we identified 37 unrelated patients with sickle cell disease (27 SS, nine SC, and one S-beta-thalassemia) of 477 unrelated sickle cell patients where the beta3 gene was linked to 20 different atypical haplotypes. These atypical chromosomes account for about 5% of the overall betaS chromosomes in this population. To investigate the origin of these atypical betaS haplotypes, we performed extensive typing of betaS and betaA chromosomes. Twenty-two different 5' subhaplotypes were identified among the betaS chromosomes. Fifteen of 20 different atypical haplotypes are likely to be the product of recombination by a single crossover around the <
Assuntos
Haplótipos/genética , Hemoglobina Falciforme/genética , Coleta de Dados , Variação Genética , Guadalupe/epidemiologia , Humanos , Mapeamento por RestriçãoRESUMO
We have studied haplotype of beta(S) chromosome and alpha-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-beta-thal (n = 56), and other rare forms (n = 10). Haplotype data on beta(S) chromosomes confirm our previous observation that Benin type is the most prevalent (75%) beta(S) chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various beta(S) haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current beta(S) haplotype distribution in this island is not distorted by haplotype-related differential survival. We also show that the frequency of alpha-thalassemia (-3.7 kb) in Guadeloupe is one of the highest recorded in this region involved in Atlantic slave trade and also failed to reveal any age-dependent increase in frequency. We conclude that the African component of Guadeloupe is distinct from that of Brazil and Cuba but is close to that of Jamaica.
Assuntos
Anemia Falciforme/genética , Globinas/genética , Talassemia alfa/genética , Adulto , Cuba , Guadalupe , Haplótipos , Humanos , Recém-NascidoRESUMO
In order to perform genetic counselling and prenatal diagnosis of Hb-S-beta-thalassemia disease and beta-thalassemia, we have delineated the spectrum of beta-thalassemia alleles in the Guadeloupean population. A sample of 63 unrelated families was analyzed including 70 beta-thalassemia carriers, 52 Hb-S-beta-thalassemia, and 8 patients with different beta-thalassemic hemoglobinopathies. Among the eleven mutations identified, four of them [-29 (A --> G), IVS-I-5 (G --> A), IVS-II-1 (G --> A), and IVS-I-5 (G --> C)] account for 77.6% of the beta-thalassemia chromosomes present in the studied families. The seven other variants, CD 24 (T --> A), IVS-I-2 (T --> C), Poly A (T --> C), -88 (C --> T), IVS- 11-849 (A --> G), Hb E, and Hb Lepore are less frequent. As a result, Hb S-beta+-thalassemia type 1 (low Hb A values: 5-15%) together with Hb S-beta(omicron)-thalassemia phenotypes are as frequent as Hb S-beta+-thalassemia type 2 (high Hb A values: 20-30%) in the Guadeloupean population. Patients with Hb S-beta+-thalassemia type 2 have milder hematological manifestations of the disease compared to patients with Hb S-beta(omicron)-thalassemia and Hb S-beta+-thalassemia type 1. This first report on the type and nature of beta-thalassemia mutations in Guadeloupe shows that prenatal diagnosis of Hb S-beta-thalassemia and beta-thalassemia should be feasible by direct detection of point mutation in most cases.
Assuntos
Globinas/genética , Talassemia beta/genética , África Ocidental/etnologia , Alelos , Anemia Falciforme/epidemiologia , Anemia Falciforme/etnologia , Anemia Falciforme/genética , Frequência do Gene , Aconselhamento Genético , Guadalupe/epidemiologia , Hemoglobina Falciforme/genética , Humanos , Índia/etnologia , Região do Mediterrâneo/etnologia , Traço Falciforme/complicações , Traço Falciforme/epidemiologia , Traço Falciforme/etnologia , Traço Falciforme/genética , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/etnologiaRESUMO
In order to delineate the spectrum of á-thalassaemia (á-thal) mutations in the Guadeloupean population, we have analysed a representative sample of 59 unrelated families carrying a á-thalassaemia trait. Using gene amplification, hybridization with 32P-labelled oligonucleotide probes and sequencing of amplified DNA, 8 different á-thal mutations were identified in 62 members of 36 families. Four of these families carried a á§-thal trait whereas, in the 32 others, a á+-thal trait has been identified. All patients were á-thal heterozygous: 30 had Hb S/á-thal, 1 had Hb C/á-thal, 1 had HPFH/á-thal whereas the remaining 30 had a Hb A/á-thal genotype. Four of the á-thal mutations detected [-29 (A -> G), IVS-I-5 (G -> C), IVS-II-1 (G -> A) and CD 24 (T -> A)] accounted for approximately 88.8 percent of the á-thalassaemia chromosomes identified. The four other variants, -88 (C -> T), IVS-I-5 (G -> A), IVS-I-5 (G -> T) and IVS-I-2 (T -> C), are less frequent. The á-thalassaemia mutations in 23 families remained unidentified and are under investigation. This study provides data for prenatal diagnosis of sickle-cell disease for Hb S/á-thalassaemia genotypes (AU)
Assuntos
Humanos , Masculino , Feminino , Talassemia beta/genéticaRESUMO
This is the first time a study has been undertaken on the HLA profile of the Martinican population, a population which is essentially the product of intermixture between African-Negroes and French Caucasians. Two hundred and thirty-eight nonrelated subjects were typed for the A and B loci, 158 subjects for C locus and 128 for DR locus. After analysis of our parameters (antigen and gene frequencies, linkage disequilibria, etc.) and their comparison to those found in the Black and Caucasian control populations, we came to the conclusion that our racially-mixed population is closer to the African-Negro population than to the French Caucasian. A study of the average gene flow enabled us to evaluate the Caucasian contribution as being about 30%. This figure is subject to change inasmuch as racial intermixture continues. Socio-cultural variables are assumed to play a minimal role, given the high rate of illegitimacy.