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M Goossens

Publications and source records attributed to M Goossens.

At least 235 records · Page 13Linked to original sources
PubMed1981

[Antenatal diagnosis of sickle-cell anaemia by DNA analysis of amniotic fluid cells. A preliminary study in the French West-Indies (author's transl)].

The genetic polymorphism previously reported to be associated with the sickle-cell (beta S) gene in black U.S.A. citizens was studied in the population of two French West-Indies islands in order to evaluate its potential application to the antenatal diagnosis of sickle-cell anaemia. The polymorphism consists of a change in the DNA sequences located near the 3' end of the beta globin gene. The change can be detected by means of the restriction endonuclease Hpa I. When cellular DNA is digested with this enzyme, the beta globin gene is contained in a DNA fragment measuring either 7.6 or 13.0 kilobases (kb). In 70% of SS homozygous subjects in Martinique and 57% in Guadeloupe the beta S gene was carried by a 13.0 kb DNA fragment, whereas the normal beta A gene was carried by a 7.6 kb DNA fragment. This polymorphism would make it possible to detect the foetal beta S gene in the DNA of amniotic fluid cells by linkage analysis.

Amniotic Fluid↗
PubMed1981

New techniques for the prenatal diagnosis of hemoglobinopathies.

Two new techniques have been devised for the prenatal diagnosis of hemoglobinopathies performed on fetal blood samples. Isoelectric focusing (IEF) of hemoglobins was compared to the classical chromatography of labelled globin chains for 51 fetal blood samples, 40 being obtained for prenatal diagnosis of hemoglobinopathies, in Paris. In all cases the two methods provided identical results. Adult hemoglobin was quantitatively evaluated. In addition blood samples obtained in other centers after abortion of 22 fetuses homozygous for beta thalassemia did not exhibited measureable amounts of Hb A by IEF. The fetal blood must be free of maternal contamination. If present maternal red blood cells can be completely eliminated by selective lysis using the 0RSKOV reaction. A chromatography of hemoglobins on Biorex 70 has been devised very recently to overcome the two limitations of IEF: First the contamination of fetal blood samples by maternal cells, and second the impossibility to evaluate Hb A when present in proportion below 1%. The chromatography of hemoglobins on Biorex 70 is performed in 75 minutes with 0.1 mg of hemoglobin present in membrane free hemolysate. The optical density recording allows to evaluate .5% of Hb A and to detect .1% of Hb A. In addition, the radioactivity profile of the chromatography can be determined. It has to be used in case of maternal contamination.

Anemia, Sickle Cell↗
PubMed1980

Triplicated alpha-globin loci in humans.

We have identified 12 individuals who are heterozygous for a chromosome with three alpha-globin genes. We determined the presence of the third alpha-globin locus by restriction endonuclease digestion and hybridization with alpha-globin cDNA probes. The three alpha-globin loci resided in an elongated fragment on digestion with EcoRI, BamHI, and Xba I, and the third locus was present in an additional 3.7-kilobase fragment on digestion with Hpa I, Sac I, and Bgl II. The locations of the restriction sites are compatible with a nonhomologous crossover mechanism producing the triple alpha loci. The frequency of the triple alpha loci was 0.0036 in American blacks and less than 0.004 in Sardinians, but was higher in Greek Crypriots (0.05). Individuals with five alpha-globin genes (alpha alpha/alpha alpha alpha) apparently showed no clinical or hematologic abnormalities.

Black People↗
PubMed1980

Prenatal diagnosis of hemoglobinopathies: comparison of the results obtained by isoelectric focusing of hemoglobins and by chromatography of radioactive globin chains.

Isoelectric focusing (IEF) of hemoglobin was compared to the classical chromatography of labeled globin chains for 22 antenatal diagnoses of hemoglobinopathies: 11 for beta thalassemia, and 11 for sickle cell disease. In all cases, the two methods gave identical results. The diagnosis was confirmed after birth or abortion. Three fetuses homozygous for beta thalassemia and one homozygous for sickle cell disease exhibited no Hb A by IEF, in contrast to normal fetuses or those heterozygous for one of the two hemoglobinopathies. In addition, blood samples obtained in other centers after abortion of 22 fetuses homozygous for beta + or beta 0 thalassemia exhibited no Hb A when analyzed by IEF. When Hb A was present, the respective proportions of Hb A and acetylated Hb F were determined by densitometry of the IEF gel. The Hb A/acetylated Hb F ratio obtained by IEF correlated well with the beta A/gamma ratio of globin chain synthesis, IEF requires 0.1 mg of unlabeled hemoglobin. It is performed in 90 min and several samples can be analyzed simultaneously. If present, maternal contamination of fetal blood must be eliminated by selective lysis of maternal (RBC) using the Orskov reaction. Improvements in this method to obtain suitable samples for IEF analysis are described.

Anemia, Sickle Cell↗
PubMed1980

The detection and use of hemoglobin mutants in the direct analysis of human globin genes.

Many human globin-chain mutants contain amino acid replacements that result from single base changes in the corresponding globin gene. Using recombinants, the coding sequences of each of the alpha-, beta-, Ggamma-, and Agamma-globin genes have now been determined. Those sequences of DNA that are cleaved by a number of specific restriction endonucleases have been identified and accurately positioned. Mutations at these sequences abolish the restriction site, and therefore, the pattern of DNA fragments containing hybridizing globin-gene sequences is altered compared to DNA from normal persons. This allows the identification of one of a pair of cross-hybridizing human globin-gene sequences, as is shown here for the two alpha-globin, the two gamma-globin, and the delta- and beta-globin genes.

Amino Acid Sequence↗
PubMed1978

[The antenatal diagnosis of haemoglobinopathies. A preliminary study (author's transl)].

From now on antenatal diagnosis of haemoglobinopathies is possible. Fetal blood can be taken from the uterus from the 17th to the 20th week of the pregnancy by direct puncture of the placenta or placentocentesis or by selective puncture of a straight vein close to its insertion in the cord on the fetal surface of the placenta, using a fetoscope. Biochemical techniques today allow us to detect beta thalassaemia major (with total absence of synthesis or with synthesis of less than 2 per cent of the beta A chain of haemoglobin by the fetus) and drepanocytosis (which is the synthesis of the chain beta S by the in the absence of production of the chain beta A). It is possible in cases where the fetal blood that has been taken is seriously contaminated by maternal blood (which is often the case with direct punctures) by using purification methods to increase the proportion of fetal red blood cells in the sample by eliminating adult reticulocytes which could cause errors in diagnosis. There are several centres where this type of diagnosis is being carried out. Some of them now have two years' experience and their results are encouraging. In spite of their difficulty these methods of investigation can allow couples at risk to have normal children or heterozygous infants. They can help them to avoid the need for termination of pregnancy or permanent contraception.

Anemia, Sickle Cell↗
PubMed1977

Properties of the double substituted hemoglobin C Ziguinchor alpha2A beta 2 6 Glu replaced by Val 58 Pro replaced by Arg.

We have previously described the structural identification of the sickle hemoglobin variant Hb C Ziguinchor (alpha2A beta2 6 Glu replaced by Val, 58 Pro replaced by Arg). This hemoglobin was found in two generations (three members) of an African family. In two family members, the clinical picture resembled that typical of a sickle cell trait, while the third member showed a more extreme clinical condition due to complication by an iron deficiency anemia. The functional properties of Hb C Zig. in red blood cells or in dilute solutions were identical to those of Hb S. The gelling behaviour of deoxy Hb C Zig. was also indistinguishable from that of Hb S. These findings suggest that, in contrast to the case of Hb C Harlem, the second substitution in position beta58 in Hb C Zig. does not interfere with the intermolecular interactions determined by the sickle substitution.

Adult↗
PubMed1976

Hemoglobin Dakar = Hb Grady: demonstration by a new approach to the analysis of the tryptic core region of the alpha chain and oxygen equilibrium properties.

Preliminary studies have suggested that in Hb Dakar, histidine alpha112 was substituted by a glutamine. A re-investigation on this hemoglobin is presented in this report. A structural study has been performed using a new approach to analyse the tryptic core region of the human hemoglobin alpha chain. After tryptic digestion of the aminoethylated alpha chain, a secondary digestion of the tryptic core was carried out with chymotrypsin and with another protease, thermolysin. Analyses of the chymotryptic and thermolytic peptides indicated that the structure of Hb Dakar was identical to that of Hb Grady previously described by Huisman et al. who showed the insertion of three amino acid residues in position alpha115 or alpha118. The insertion, which was localized near two residues involved in the alpha1beta1 contact, did not produce a dissociation into dimers. Functional studies demonstrated a a slightly increased oxygen affinity, a lowered cooperativity and a normal Bohr effect. The low amount of the abnormal hemoglobin (8%) may in part be explained by a slight instability of the molecule.

Amino Acid Sequence↗
PubMed1976

Hemoglobin J Cairo: beta 65 (E9) Lys leads to Gln, A new hemoglobin variant discovered in an Egyptian family.

The present report describes clinical, hematological and biochemical studies of a 27-year old Egyptian woman in whom a fast moving Hb variant was found. The abnormal Hb constituted 48% of the total erythrocyte Hb of the propositus and her father. Structural studies demonstrated that in the abnormal Hb lysine beta 65 is replaced by glutamine. The new Hb mutant is designated hemoglobin J Cairo beta 65 (E9) Lys leads to Gln. This substitution results in only a moderate decrease in cooperativity. No evidence of Hb instability was found. A slight anemic state has been observed in the propositus since she reached adolescence.

Adult↗