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Biomedical subjects

J M Old

Publications and source records attributed to J M Old.

At least 55 records · Page 3Linked to original sources
PubMed1988

The role of cloned genes in the prevention of genetic disease.

The application of recombinant DNA technology to the study of human genetic disease promises to increase the scope for carrier detection and prenatal diagnosis. Here we summarize current experience with prenatal diagnosis of single-gene disorders by DNA analysis and highlight some of the technical and organizational problems that remain to be solved.

Cloning, Molecular↗
PubMed1988

Evidence linking familial thrombosis with a defective antithrombin III gene in two British kindreds.

Using DNA probes in a structural study of the antithrombin III gene locus we found no evidence of gene deletion in two British kindreds with inherited antithrombin III deficiency. However, linkage analysis between a common DNA polymorphism and the antithrombin III deficiency trait showed that the defect lies at or close to the antithrombin III structural gene. The lod score for linkage within the larger Scottish kindred was 3.1 (theta = 0). These results are consistent with previously published data suggesting that mutation of the antithrombin III structural gene is the cause of inherited antithrombin III deficiency in some families.

Antithrombin III↗
PubMed1987

Association of thalassaemia intermedia with a beta-globin gene haplotype.

We have identified 14 Asian patients with homozygous beta zero thalassaemia who had a mild clinical disorder related to an augmented production of haemoglobin F. None of their parents had an elevated level of Hb F. Restriction fragment length polymorphism analysis of the beta-globin cluster of these patients and a control group of Asian thalassaemia major patients showed that 6/14 of the thalassaemia intermedia patients were homozygous for a particular 5' beta-globin haplotype (-+-++), in contrast to 1/42 of the thalassaemia major patients. Furthermore, the -+-++ beta haplotype is also associated with amelioration of disease severity in beta thalassaemia in an Italian population. This beta haplotype is linked to a DNA sequence variation 5' (at position -158) to the G gamma globin gene which can be detected by the presence (+) of an Xmn I restriction enzyme site. The possible role of the Xmn I-gamma polymorphism in relation to this variant HPFH is discussed. We conclude that much of the observed clinical variability of beta thalassaemia can now be explained by the inheritance of beta thalassaemia chromosomes with different propensities for fetal haemoglobin production.

Adolescent↗
PubMed1986

First-trimester fetal diagnosis for haemoglobinopathies: report on 200 cases.

First-trimester prenatal diagnosis by DNA analysis was found to be possible in 224 (80%) of 281 families at risk of having a child with beta-thalassaemia major. 200 prenatal diagnoses, mainly for beta-thalassaemia or sickle-cell anaemia, were made by means of chorionic villus sampling and fetal DNA analysis. The overall fetal loss rate was 6.7%, the majority being in the first half of the programme. There was one misdiagnosis. Prenatal diagnosis was also carried out successfully for both pairs of twins in two pregnancies. Comparison of these results with 53 prenatal diagnoses made with DNA prepared from amniotic fluid suggests that the first-trimester procedure is more reliable. If further experience confirms that chorionic villus sampling has an acceptably low risk for both mother and fetus it will largely replace other methods for prenatal diagnosis of the haemoglobin disorders and other single-gene conditions.

Amniotic Fluid↗
PubMed1986

Meiotic recombination between two polymorphic restriction sites within the beta globin gene cluster.

Analysis of beta globin gene haplotypes for prenatal diagnosis of beta thalassaemia has revealed a recombination event within the beta globin gene cluster. Both a change in the AvaII polymorphic site within the beta globin gene and a change in the phenotype of the beta globin gene were observed. Paternity was established by the pedigree analysis of hypervariable 'minisatellite' DNA polymorphisms and the most probable explanation of the recombination event is a crossover between the psi beta globin gene and the beta globin gene. The data provide direct evidence in support of a DNA region 3' to the beta globin gene with a recombination frequency much higher than expected, and have important implications for the prenatal diagnosis of beta thalassaemia by linked restriction fragment length polymorphisms.

Alleles↗
PubMed1986

Prenatal diagnosis of Duchenne muscular dystrophy by DNA analysis.

Linkage studies have been carried out in 20 families segregating for Duchenne muscular dystrophy and eight prenatal diagnoses performed, including six first trimester diagnoses and one twin pregnancy. The results of the restriction fragment length polymorphism (RFLP) analysis suggest that not all the possible RFLPs need to be used and a strategy for carrier detection studies is proposed.

DNA↗
PubMed1985

Feasibility of prenatal diagnosis of beta-thalassaemia with synthetic DNA probes in two Mediterranean populations.

A feasibility study in two Mediterranean populations showed that prenatal diagnosis of beta-thalassaemia with a limited number of synthetic oligonucleotide probes would have been possible in about 70% of cases. To provide a comprehensive programme of prenatal diagnosis for the thalassaemias it would be necessary, in most populations, to combine fetal DNA analysis with fetal blood sampling and globin-chain synthesis studies.

Autoradiography↗
PubMed1985

Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis.

Direct gene analysis was used in the prenatal exclusion of ornithine transcarbamylase (OTC) deficiency; karyotyping the family's previously affected child had already identified the defect as a small deletion. A cloned OTC gene and two other X chromosome-specific probes were mixed, and hybridised to fetal DNA obtained from cultured amniocytes; the fetus was shown to be a normal male.

Adult↗
PubMed1985

Segregation analysis of a marker localised Xp21.2-Xp21.3 in Duchenne and Becker muscular dystrophy families.

A DNA marker C7, localised Xp21.1-Xp21.3, has been studied in kindreds segregating for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). In DMD families four crossovers were observed in 38 informative meioses between C7 and the DMD locus (theta = 0.12, z max = +2.72). In BMD families no recombinants were observed in the 16 informative meioses studied. These data are consistent with the localisation of the mutations in these disorders being in the same region of Xp21. Studies in families also segregating for the DNA marker 754 support the previously reported physical order of these loci as X centromere-754-DMD-BMD-C7-X telomere. A recombination fraction of 0.11 (z max = +5.58) was found between DMD-754 by combining our previously published data with the data presented here. C7 and 754 thus provide good bridging markers for the diagnosis of DMD and BMD.

Chromosome Banding↗
PubMed1985

The sequence of the A gamma globin gene in a G gamma beta+ type of hereditary persistence of fetal haemoglobin.

The sequence of the A gamma globin gene from the affected chromosome of an individual heterozygous for the G gamma beta+ type of hereditary persistence of fetal haemoglobin (G gamma beta+ HPFH) is reported. With two exceptions, it is identical to one of the two allelic A gamma globin genes already sequenced and there is therefore no change which could explain the absence of its expression in the face of the persistent G gamma globin expression which is a feature of this condition.

Alleles↗