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D J Shaw

Publications and source records attributed to D J Shaw.

At least 91 records · Page 5Linked to original sources
PubMed1990

Linkage relationships of the apolipoprotein C1 gene and a cytochrome P450 gene (CYP2A) to myotonic dystrophy.

We have studied the genetic linkage of two markers, the apolipoprotein C1 (APOC1) gene and a cytochrome P450 (CYP2A) gene, in relation to the gene for myotonic dystrophy (DM). A peak lod score of 9.29 at 2 cM was observed for APOC1-DM, with a lod score of 8.55 at 4 cM for CYP2A-DM. These two markers also show close linkage to each other (theta max = 0.05, Zmax = 9.09). From examination of the genotypes of the recombinant individuals, CYP2A appears to map proximal to DM because in one recombinant individual CYP2A, APOC2 and CKMM had all recombined with DM. Evidence from another CYP2A-DM recombinant individual places CYP2A proximal to APOC2 and CKMM. Localisation of CYP2A on a panel of somatic cell hybrids also suggests that it is proximal to DM and APOC2/C1/E gene cluster.

Apolipoprotein C-I↗
PubMed1990

A 90 kb DNA deletion associated with neurofibromatosis type 1.

A deletion of 90 kb of DNA has been identified in a patient with neurofibromatosis type 1, using pulsed field gel electrophoresis. The deletion lies between probes 17L1A and AC5 in the critical region of chromosome 17 and represents the only molecular alteration found by PFGE in a series of 90 unrelated patients. The subject showing the deletion is an isolated case, shows typical clinical features, and represents one of the first examples of a molecular deletion to be found in this disorder.

Chromosome Deletion↗
PubMed1989

Long-range restriction map of a region of human chromosome 19 containing the apolipoprotein genes, a CLL-associated translocation breakpoint, and two polymorphic MluI sites.

The apolipoprotein gene cluster on human chromosome 19 (APOC1, APOC2, APOE) has been localised by pulsed-field gel electrophoresis to within 200 kb of a chronic lymphocytic leukemia-associated translocation breakpoint. A restriction map covering 1300 kb around these loci has been constructed and contains two polymorphic MluI sites, which appear to show Mendelian inheritance. The orientation of the map on the chromosome has been established as 19cen - CLL breakpoint - APOC2 - 19qter. Pedigree analysis using APOC2, a probe derived from the CLL breakpoint, and other localised markers on 19q suggests that the myotonic dystrophy locus is distal to APOC2 on 19q.

Apolipoproteins↗
PubMed1989

Myotonic dystrophy: developments in molecular genetics.

Myotonic dystrophy, the commonest muscular dystrophy of adult life and the most variable of all muscular dystrophies follows autosomal dominant inheritance and is determined by a genetic locus on chromosome 19. The development of DNA probes on this chromosome, some of them representing specific genes, has provided a series of closely linked markers for myotonic dystrophy, which together with the construction of a series of somatic cell hybrid lines has allowed a detailed localization on the long arm of the chromosome. Existing markers are already able to provide accurate tests of genetic prediction, including prenatal diagnosis. Analysis of the relevant region of 19q by pulsed field gel electrophoresis and other molecular techniques is now in progress to identify the myotonic dystrophy gene itself.

Chromosome Mapping↗
PubMed1989

Linkage disequilibrium in Huntington's disease: an improved localisation for the gene.

The search for the Huntington's disease gene has recently concentrated on the telomere of the short arm of chromosome 4. The evidence suggesting this position has been based on single crossover events, but there is conflicting evidence regarding the position of the gene relative to the most terminal markers. We have found significant linkage disequilibrium between the markers D4S98 (probe BS731B-C) and D4S95 (probe BS674E-D) and HD, which supports a localisation for the gene proximal to D4S90 and makes a telomeric localisation unlikely. This disequilibrium may also prove to be important in the future in allowing modification of risk estimates based on genetic linkage.

Alleles↗
PubMed1987

Further mapping of markers around the centromere of human chromosome 19.

The gene for myotonic dystrophy (DM) is located on the proximal long arm of chromosome 19 along with at least 10 cloned genes and anonymous DNA segments. In order to refine the map of this region of the chromosome, we have constructed somatic cell hybrid lines from fibroblasts carrying a balanced translocation t(1, 19) with a breakpoint at 19q12. We have established that D19S7 is the most proximal of the available long-arm markers and confirmed that PEPD localizes to 19q, along with PVS, MSK19, and MSK37. We have also examined the segregation of markers from the proximal long-arm region of chromosome 19 in hybrids containing fragments of this chromosome.

Animals↗
PubMed1987

Localisation on human chromosome 19 of three genes for cell surface antigens defined by monoclonal antibodies.

Expression of three distinct human cell surface antigens defined by monoclonal antibodies (mAbs) was examined in a series of rodent-human somatic cell hybrids retaining different subsets of human chromosomes. Cell surface reactivity with mAbs F8 and G253, detecting a 95 kilodalton (kD) glycoprotein (gp95); with mAbs F10 and A103, detecting a 50 kD glycoprotein (gp50); and with mAb S7 was found to cosegregate with human chromosome 19. However, differential antigen expression was observed with hybrids containing fragments of the 19 and hybrids constructed with different human cell types. Comparison of results from the serological typing with the presence of a number of chromosome 19 DNA markers in hybrid cells and cytogenetic analysis suggests that MSK20, the gene coding for the F10/A103 antigen gp50, is located in chromosome region 19pter----19p13.2. The genes coding for the F8/G253 antigen, gp95 (gene symbol MSK19) and the S7 antigen (MSK37) are located in region 19p13.2----19q13.2. Thus, the cell surface antigens described in this study may be used as selectable markers for specific portions of human chromosome 19.

Animals↗
PubMed1986

Application of a closely linked polymorphism of restriction fragment length to counselling and prenatal testing in families with myotonic dystrophy.

The close genetic linkage between the loci for apolipoprotein CII (ApoC2) and myotonic dystrophy makes ApoC2 the closest fully validated marker for prediction of myotonic dystrophy. Application to genetic counselling and presymptomatic and prenatal prediction is reported in seven families with myotonic dystrophy, including one case in which the disorder was excluded prenatally. Only one of the families did not have members with ApoC2 genotypes that allowed prediction, but careful clinical study of older family members was found to be an important factor. ApoC2 typing of families with myotonic dystrophy should be of practical help both in prediction for asymptomatic relatives and for prenatal diagnosis in pregnancies of an affected parent.

Adult↗
PubMed1986

Studies of a DNA marker (G8) genetically linked to Huntington disease in British families.

Close genetic linkage has been shown between the DNA sequence G8 (locus D4S10) and 16 British families with Huntington disease using the HindIII, EcoR1, Nci1, and Pst1 polymorphisms detected by G8, and by combining all the polymorphisms to give a combined haplotype. Two recombinants have been detected in these families giving a maximum lod score of 17.60 at a theta of 0.02. These results confirm the originally reported linkage between the loci and provide evidence against significant multilocus heterogeneity for Huntington disease.

Alleles↗
PubMed1986

Regional localisations and linkage relationships of seven RFLPs and myotonic dystrophy on chromosome 19.

We have studied the genetic linkage relationships of seven DNA polymorphisms on chromosome 19, with each other and with the myotonic dystrophy locus. The DNA sequences were localised to various regions of the chromosome using translocations in somatic cell hybrids. These results provide the basis for a linkage map of most of chromosome 19, and suggest that the myotonic dystrophy locus is close to the centromere.

Animals↗
PubMed1986

Linkage relationships of the insulin receptor gene with the complement component 3, LDL receptor, apolipoprotein C2 and myotonic dystrophy loci on chromosome 19.

Myotonic dystrophy is associated with disturbances in the insulin response, possibly due to an abnormality of the insulin receptor. Both the myotonic dystrophy (DM) and insulin receptor (INSR) genes are on chromosome 19. Using a cloned gene probe for INSR, we have studied its linkage relationships with the DM locus and other chromosome 19 markers. The results show that INSR is not closely linked to DM, but is located very close to C3, in the region 19pter-19p13.2. This implies that the basic genetic defect which causes DM is not directly responsible for the disturbed insulin response in these patients.

Apolipoprotein C-II↗
PubMed1986

Mapping human chromosomes in somatic cell hybrids using a low-copy-number repetitive sequence.

We have isolated a human-specific repetitive sequence with a copy number of several hundred (p11L26). Using Southern blots of EcoR1-digested DNA from somatic cell hybrids containing one or a few human chromosomes, band patterns specific for those chromosomes can be generated by hybridization with p11L26. Genomic copies of the sequence have also been mapped to subchromosomal regions using translocations. The probe offers a useful addition to the standard techniques for mapping human chromosomes in hybrid cell lines.

Animals↗