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Biomedical subjects

M Bobrow

Publications and source records attributed to M Bobrow.

At least 145 records · Page 8Linked to original sources
PubMed1988

Chromosome banding in direct preparations of chorionic villi.

Chorionic villus sampling (CVS) is now currently offered for first trimester prenatal diagnosis of genetic disorders. Chromosome analysis of CVS in direct and culture preparations is possible using modifications of standard banding techniques. We summarize our experience in applying QFQ, GTG, RBG, CBG, DA/DAPI, NOR, and SC differentiation protocols to direct preparations. Characteristic chromosome regions are properly labelled by these techniques, and analysis of 300 band stage karyotypes is consistently achievable on GTG banded direct preparations. However, banding of CVS direct chromosomes has proved to be difficult, and the analysis needs to be backed up by culture preparations.

Chorionic Villi↗
PubMed1988

Cystic fibrosis typing with DNA probes: experience of a screening laboratory.

A sample of 125 individuals from 37 British cystic fibrosis (CF) families with at least one living affected child were typed with probes for restriction fragment length polymorphisms (RFLPs) known to be linked to the CF gene. These probes were MetD, MetH, pJ3.11 and 7C22. Using this combination of probes, 30 out of the 37 families were sufficiently informative to enable prenatal diagnosis of the disease. Linkage analysis has also proved to be useful in excluding CF in two cases where diagnosis of the disease was equivocal in the sibling of an affected child.

Alleles↗
PubMed1988

Cell cycle studies in chorionic villi.

We have studied the cell cycle of cells obtained from chorionic villi in direct and culture preparations by incorporation of the thymidine analogue BrdU to produce late-labelling or sister chromatid differentiation patterns. We have, therefore, been able to estimate the duration of the cell cycle and, more specifically, the length of some of its phases. While results for chorionic villus sample cells in culture resembled those obtained for fibroblasts, data for the spontaneously dividing trophoblastic cells in direct preparations were different. Villi exposed to BrdU immediately after sampling showed a slight delay in the incorporation of the analogue and a lower percentage of labelled cells compared to villi treated after an overnight incubation, probably due to a temporary effect of the sampling technique. Results from semi-direct protocols suggest that cells have a G2 of no more than 4 h, and a mid-S phase of 10-16 h. The G1 period is very variable. After 48 h incubation with BrdU, only 4% of cells reach their second generation, whereas this percentage increases up to 70% after 72 h, indicating that under these experimental conditions most cells have a cell cycle of approximately 36 h. The average number of sister chromatid exchanges was similar in both direct preparations and cultures: 5.2 +/- 2.1 SCE per cell.

Cell Cycle↗
PubMed1988

The application of molecular biology to the prenatal diagnosis of renal disease.

The rapid development of new techniques in molecular biology is leading to identification of the genes responsible for a wide variety of diseases. Several renal conditions are caused by gene defects and are amenable to this approach. The process of gene mapping is discussed and the current position regarding prenatal diagnosis and carrier testing for genetic renal disease is reviewed.

DNA↗
PubMed1988

A deletion hot spot in the Duchenne muscular dystrophy gene.

We have made a detailed study of a deletion hot spot in the distal half of the Duchenne muscular dystrophy (DMD) gene, using intragenic probe P20 (DXS269), isolated by a hybrid cell-mediated cloning procedure. P20 detects 16% deletions in patients suffering from either DMD or Becker muscular dystrophy (BMD), in sharp contrast to the adjacent intragenic markers JBir (7%) and J66 (less than 1%), mapping respectively 200-320 kb proximal and 380-500 kb distal to P20. Of the P20 deletions, 30% start within a region of 25-40 kb, the majority extending distally. P20 was confirmed to map internal to a distal intron of the DMD gene. This region was recently shown by both cDNA analysis (M. Koenig et al., 1987; Cell 50: 509-517), and field inversion electrophoresis studies (J.T. Den Dunnen et al., 1987, Nature (London) 329: 640-642) to be specifically prone to deletions. In addition, P20 detects MspI and EcoRV RFLPs, informative in 48% of the carrier females. Together, these properties make P20 useful for carrier detection, prenatal diagnosis, and the study of deletion induction in both DMD and BMD.

Cell Line↗
PubMed1988

The gene for incontinentia pigmenti: failure of linkage studies using DNA probes to confirm cytogenetic localization.

Probes for restriction fragment length polymorphisms mapping between Xp21 and Xq22.3 have been used in a linkage study of incontinentia pigmenti (IP). Six independent sporadic cases of disorders resembling IP with X-autosome translocations involving the same X chromosome breakpoint (Xp11) have been reported. These observations suggest that the IP gene may be located in the Xp11 chromosomal region. However, the linkage study with DNA probes has failed to confirm this localisation.

Chromosome Mapping↗
PubMed1988

PRUFILE: a clinical and laboratory database for the genetics centre.

The growing complexity and volume of workload in a Clinical Genetics Centre can rapidly swamp the available clerical facilities. The multiuser database described gives facilities not only for administrative control and documentation but also for the production of data for clinical and scientific analysis. The close link between clinical and laboratory databases gives great versatility and easy expansion as new tests and disciplines are applied to clinical genetic problems.

Clinical Laboratory Information Systems↗
PubMed1987

DNA deletions in mild and severe Becker muscular dystrophy.

The DNA of 33 patients diagnosed as suffering from Becker muscular dystrophy (BMD) has been probed with cloned DNA sequences from Xp21, known to reveal DNA deletions in patients suffering from the more severe Duchenne muscular dystrophy (DMD). Two BMD cases showed clear deletions. A third case gave aberrant band sizes, which further analysis showed to be caused by a small deletion. This suggests that deletions in DXS164 occur approximately as frequently in BMD as they do in DMD. Of the two cases showing large deletions, one is at the severe end of the Becker clinical spectrum, whilst the other is a classical Becker-type dystrophy. The fact that loci defined by probes commonly deleted in classical DMD patients are also deleted in BMD patients of varying severity is strong additional evidence that these disorders are allelic, and further justifies the use of probes with defined linkage relationships to DMD also being used for counselling in BMD families.

Adolescent↗
PubMed1987

Prenatal diagnosis of X-linked choroideremia with mental retardation, associated with a cytologically detectable X-chromosome deletion.

We describe a family in which an X-chromosome deletion is segregating with choroideremia, and X-linked recessive condition. The DNA sequences DXYS1 and DXS3, defined by the probes pDP34 and 19.2 respectively, are absent in the affected male (who is also mentally retarded), and hemizygous in his mother and in his carrier sister, who presented early in pregnancy. Analysis of chorionic villus DNA formed the basis of prenatal exclusion of choroideremia in her male fetus. In three female relatives, studied with late-labelling techniques, the deleted X was preferentially inactivated in 86-100% of cells studied. This family confirms the localisation of the choroideremia locus to within Xq13----21, and places the loci for anhidrotic ectodermal dysplasia and the X-linked immunodeficiencies outside this region.

Choroid↗
PubMed1987

A small deletion in the Duchenne/Becker muscular dystrophy locus--a functionally important region?

A DNA deletion in a patient with Becker muscular dystrophy (BMD) has been delineated by restriction endonuclease mapping. The deletion is unusually small, removing six kilobases (kb) of DNA distal to pERT 87-1 (DXS164). This region has previously been shown to contain an exon of a candidate gene which, when defective, causes Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy. Removal of this exon and surrounding DNA is apparently sufficient, in this case, to cause a BMD phenotype. The occurrence of this deletion in DXS164 would appear to confirm that this region is part of the BMD locus. Many DMD patients have deletions in and around this region, adding further evidence for the allelic nature of the two disorders. This fortuitous deletion may identify a functionally important domain of the protein product in terms of the severity of phenotype manifested.

Chromosome Deletion↗
PubMed1987

The application of linkage analysis to genetic counselling in families with Duchenne or Becker muscular dystrophy.

A total of 278 families of probands with Duchenne or Becker muscular dystrophy has been ascertained and offered genetic counselling. Linkage studies have been performed in these families using polymorphic DNA markers identifying loci linked to Duchenne and Becker muscular dystrophy. The clinical features of the probands are discussed: there was marked intrafamilial resemblance in the severity of the disease. We estimate that a complete study of potential carriers in these families would require analysis of samples from approximately 1400 subjects. The results of linkage studies tended to move women's carrier risk estimates (based on CK and pedigree data) towards the extremes of the risk categories, providing a more definitive risk estimate for 81% of the women who were previously in the middle range of carrier risk probabilities. About 70% of the families had only one affected member. Linkage analysis altered carrier risk estimates in 95% of sisters and aunts of index cases, but only affected estimates of the mother's carrier risks in about 11% of isolated cases. Even where linkage studies were not helpful in elucidating carrier risks, information could usually be obtained for use in prenatal diagnosis if required. We have assessed the attitudes to pregnancy and prenatal diagnosis of women at risk of being carriers of Duchenne or Becker muscular dystrophy and report 17 pregnancies in these women.

Amniocentesis↗
PubMed1986

A balanced de novo X/autosome translocation in a girl with manifestations of Lowe syndrome.

The Oculo-cerebro-renal syndrome of Lowe is an X-linked recessive disorder characterised by mental and growth retardation, renal rickets with renal tubular acidosis, generalised aminoaciduria, hypotonia, cataracts, glaucoma and frontal bossing. Manifestations of this syndrome were seen in a girl with no family history of the disorder, but who was found to have a de novo balanced X/3 translocation, with a breakpoint at Xq25. She had also inherited a balanced 14/17 translocation from her father. It is postulated that the clinical picture may be the result of disruption of the X chromosome within the gene at the locus for Lowe syndrome, with non-random inactivation of the normal X, which may permit the expression of this X-linked recessive disorder in a girl.

Child↗
PubMed1986

A linkage study of Emery-Dreifuss muscular dystrophy.

We have searched for linkage between polymorphic loci defined by DNA markers on the X chromosome and X-linked Emery-Dreifuss muscular dystrophy (EDMD). There are high recombination rates between EDMD and the Xp loci known to be linked to Becker and Duchenne muscular dystrophy. There is a suggestion of linkage between EDMD and the loci DXS52 and DXS15, defined by probes St14 and DX13 respectively, located at Xq28. Z for DXS15 = 1.14 at theta = 0.15. This is in agreement with the previously reported linkage between a disorder strongly resembling EDMD and colour-blindness (Thomas et al. 1972), suggesting that there is a second locus on the X chromosome concerned with muscle integrity.

Adolescent↗
PubMed1986

The screening of Duchenne muscular dystrophy patients for submicroscopic deletions.

We have probed the DNA of 156 Duchenne muscular dystrophy (DMD) patients, representing 140 kindreds, with cloned DNA sequences derived from Xp21 and known to show deletions in some DMD patients. Sixteen cases showed a deletion, as defined by lack of hybridisation to one or more of the four probes used. However, two of these cases were brothers, so 15 independent deletions (10.7%) are represented. The deletion map is compatible with the suggested order for the sites of the probes used in the study, that is, telomere----pERT87.15----pERT87.8----pERT87.1----pX J1.1----754----centromere. Further mapping of these deletions and characterisation of the deletion breakpoints should facilitate more accurate molecular localisation of the gene or genes which, when mutated, are responsible for causing DMD.

Chromosome Deletion↗
PubMed1986

Linkage studies in Duchenne and Becker muscular dystrophies.

We have studied the inheritance of four cloned DNA sequences which recognise restriction fragment length polymorphisms on the short arm of the X chromosome in families with Becker and Duchenne muscular dystrophy. We have confirmed linkage of two probe loci to the disease loci and have combined our results with those previously published to give a maximum lod score of 11.642 at a recombination fraction of 0.15 for DXS41 (probe 99.6), and a maximum lod of 15.84 at a recombination fraction of 0.15 for DXS84 (probe 754). Linkage of these diseases to the loci defined by the pERT87 probes and probe pXJ1.1 has also been studied, giving maximum lod scores of 8.634 and 5.118 at recombination fractions of 0.02 and 0.00 respectively. The information obtained using these polymorphic DNA markers, combined with pedigree and CK data, can be used to give more accurate genetic counselling to women at risk in Becker and Duchenne families.

DNA↗