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C Beldjord

Publications and source records attributed to C Beldjord.

101 records · Page 6Linked to original sources
PubMed1984

Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa.

Previous studies of the Hpa I cleavage site-sickle cell hemoglobin gene linkage in various African populations suggested that the sickle gene arose independently more than once. In the present study we have performed restriction endonuclease haplotype analysis for the beta-globin-like gene cluster from four separate geographic areas in Africa, all of which possess the sickle gene. In Benin (Central West Africa) and Algeria (Arab North Africa) all chromosomes carrying the sickle gene possess an identical haplotype as defined by 11 different polymorphic restriction endonuclease sites within the 60-kilobase region of the beta-globin-like gene cluster. In the Central African Republic (Bantu-speaking Africa) and in Senegal (Atlantic West Africa) a very large proportion of the sickle gene chromosomes were associated with a haplotype specific for each country. Thus, three different haplotypes are shown to be associated with the sickle gene in Africa, and each is present at a very high frequency in geographically separate regions. Since the three haplotypes differ from each other by at least three sites residing both 5' and 3' to a putative hot spot for recombination, it is most likely that the sickle gene arose at least three times on separate preexisting chromosomal haplotypes. This may have implications for a better understanding of the variable nature of the expression of sickle cell anemia, because clinically relevant sequences (for example, gamma-globin gene regulatory sequences responsive to anemia) might be linked polymorphically to these haplotypes.

Africa↗
PubMed1984

Linkage between fetal A gamma globin chain polymorphism and DNA polymorphism of the human beta gene cluster in beta thalassaemia.

The association between the polymorphism of the A gamma chain of human fetal haemoglobin and the DNA polymorphism at the beta gene cluster has been investigated. The A gamma 75 threonine mutation was found in association with haplotypes II and VI described by Orkin et al. (1982), which share the HindIII cleavage site in the A gamma IVS 2 sequence. The distance between the two polymorphic sites is 868 base-pairs. In contrast, haplotypes I, III, V and IX which do not possess this HindIII cleavage site were associated with the normal A gamma 75 isoleucine allele. The simple detection of the gamma gene polymorphism at the protein level can be useful for identifying DNA haplotypes, and therefore beta thalassaemic mutations.

Chromosome Mapping↗
PubMed1983

Four new haplotypes observed in Algerian beta-thalassemia patients.

beta-Thalassemia, a heterogeneous group of human anemias affecting the expression of beta-globin, is caused by a number of molecular defects. Restriction endonuclease mapping of ethnic populations has revealed many polymorphisms within and around the beta-like globin genes, combinations of which are assigned as haplotypes. Several haplotypes appear to be strongly linked with the molecular defects causing thalassemia in Greek and Italian patients (Orkin et al. 1982). We describe here haplotypes from 40 Algerian beta-thalassemic patients and eight normals determined by restriction endonuclease mapping at seven polymorphic sites. Four haplotypes previously unreported were observed in these thalassemic patients; this argues the existence in this population of undescribed beta-thalassemia alleles. The knowledge of the haplotypes in thalassemic families could be used for prenatal diagnosis of homozygote forms.

Algeria↗
PubMed1981

The sickle gene polymorphism in North Africa.

Analysis of the restriction endonuclease Hpa 1-beta globin gene linkage has been performed in a predominantly Arab population of North Africa possessing the sickle (beta A) gene is found associated with a 7.6 kilobase) or 7.0 kb Hpa 1 fragment (54/54 assignable beta A genes), whereas the beta S gene is found associated with a 13 kb Hpa 1 fragment (42/42 assignable beta S genes). The results demonstrate a very tight linkage of the beta S gene to the 13 kb Hpa 1 fragment as well as a very low probability that a beta A gene will be found on a 13 kb Hpa 1 fragment. Thus, the North African population presents a nearly ideal opportunity for prenatal diagnosis solely by Hpa 1-beta globin gene linkage analysis. Additionally, the evidence supports the hypothesis that the beta S gene flowed from West Africa rather than from Arab populations in the Middle East.

Africa, Northern↗
PubMedDate not supplied

Determination of the gene structure of human oligophrenin-1 and identification of three novel polymorphisms by screening of DNA from 164 patients with non-specific X-linked mental retardation.

We have recently shown that mutations in oligophrenin-1 (OPHN1) are responsible for non-specific X-linked mental retardation (MRX). The structure of the gene encoding the OPHN1 protein was determined by isolation of genomic DNA clones from the human cosmid library. Genomic fragments containing exons were sequenced, and the sequences of the exons and flanking introns were defined. Knowledge of the genomic structure of the OPHN1 gene, which spans at least 500 kb and consists of 25 exons, will facilitate the search for additional mutations in OPHN1. OPHN1 was screened for mutations in 164 subjects with non-specific mental retardation. Three nucleotide substitutions were identified, one of which was a silent mutation in the codon threonine 301 at position 903 (G-->C). The other substitutions were located in exon 2, a G-->A substitution at position 133 (A45T), and in exon 10, a C-->T substitution at position 902 (T301M), but these are common polymorphisms rather than disease-causing mutations.

Amino Acid Substitution↗
PubMedDate not supplied

A splicing mutation in intron 16 of the cystic fibrosis transmembrane conductance regulator gene, associated with severe disease, is common on Reunion Island.

In addition to the frequent delta F508 and Y122X mutations on cystic fibrosis (CF) chromosomes of patients from Reunion Island, one splicing mutation, 3120+1G-->A is observed relatively frequently (12.5%) in this group, in comparison with the French metropolitan population (<0.001 %). This mutation, disrupting the 5' splice donor site of intron 16, can be detected easily by restriction enzyme BstNI digestion. In 2 CF patients homozygous for this mutation, the clinical pattern was severe, with both pancreatic insufficiency and respiratory symptoms.

Child↗
PubMedDate not supplied

[Molecular analysis and prenatal diagnosis of beta-thalassemia: about our experience in central Tunisia].

Beta-thalassemia, by its high frequency and its heterogeneity, constitutes a real problem of health in Tunisia. Prenatal diagnosis by DNA analysis represents the only reality for couples at risk. The denaturant gradient (urea and formamide) on polyacrylamide gel electrophoresis has been performed in our laboratory, using psoralen as chemical clamps. This method is simple, reliable, safe, rapid, without radioactivity and has a reasonable cost (chemical clamps). Even if it needs an informatic modelization in other laboratories, this method seems to be adapted to our economic and work conditions and to the molecular heterogeneity of the Tunisian beta-thalassemia. We present the results of an epidemiological molecular study on 75 patients with beta-thalassemia and the results of ten prenatal diagnosis. The molecular lesions codon 39 (C-T) and IVS1 nt2 (T-G) are the most frequent in our study. This technical approach provides genetic counselling for at risk families by offering prenatal diagnosis (reducing as possible the cost and the delay of the result) after prealable family study and identification of the mutation(s).

Codon↗
PubMedDate not supplied

Mapping of the X-breakpoint involved in a balanced X;12 translocation in a female with mild mental retardation.

Balanced chromosomal abnormalities such as translocations and inversions have been identified in many genetic diseases. Cloning of the breakpoints involved in these abnormalities has led to the identification of the disease-related genes. Recent reports suggest the presence of a mental retardation locus at Xq11-12. We have identified a female patient with a balanced translocation t (X;12) (q11;q15) associated with mild mental retardation. We identified a yeast artificial chromosome spanning the X-chromosome breakpoint by using fluorescent in situ hybridization techniques. A cosmid library of this YAC has been constructed and the search for candidate genes is in progress.

Child↗