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R Williamson

Publications and source records attributed to R Williamson.

At least 397 records · Page 22Linked to original sources
PubMed1984

Familial apolipoprotein CII deficiency: a preliminary analysis of the gene defect in two independent families.

We have used a cDNA clone for human apolipoprotein CII (apo CII) to study the apo CII genes in two independent individuals with familial apo CII deficiency. With all the restriction enzymes so far used, gene fragments hybridising with apo CII cDNA are observed that are indistinguishable from normal samples. This demonstrates that in neither of these individuals is the defect due to a major deletion of DNA in or around the apo CII gene. We have used a common polymorphism of the apo CII gene detected with the enzyme TaqI to follow the inheritance of the gene in the families of these apo CII deficient individuals. The pattern of inheritance that we observe is consistent with the defect causing apo CII deficiency being in, or closely linked to the apo CII structural gene.

Apolipoprotein C-II↗
PubMed1984

Use of a chromosome 21 cloned DNA probe for the analysis of non-disjunction in Down syndrome.

A recombinant clone was isolated containing a sequence which occurs only on human chromosome 21 and defines a two-allele restriction fragment length polymorphism showing Mendelian inheritance. Forty seven percent of the London population are heterozygous for the polymorphism. The chromosomal location of the DNA sequence homologous to the probe was confirmed using rodent-human somatic cell hybrids. DNA from persons with Down syndrome and from their parents was analysed. It was possible to confirm trisomy 21 by dosage hybridisation to Southern blots, and to determine the origin of the supernumerary chromosome. The technique will be of use for determination of the paternal or maternal origin of nondisjunction in cases of Down syndrome which are not informative using existing markers.

Adult↗
PubMed1984

The identification of a DNA polymorphism of the alpha fibrinogen gene, and the regional assignment of the human fibrinogen genes to 4q26-qter.

We have identified a common restriction fragment length polymorphism of the alpha fibrinogen gene with the enzyme TaqI. This polymorphism is probably due to a single base change that creates or destroys a TaqI recognition site about 1000 basepairs from the 3' end of the alpha fibrinogen géne. The frequency of the rare allele in 83 unrelated healthy individuals is 0.33. We have used in situ hybridisation of the alpha fibrinogen cDNA to localise the gene on chromosome 4q29-31. We have confirmed this regional localisation by restriction fragment detection in a human X Chinese hamster somatic cell hybrid which contains a translocated human chromosome 4 with a breakpoint at 4q26. The alpha, beta, and gamma fibrinogen genes are all present on human chromosome 4q26-qter.

Base Sequence↗
PubMed1984

The positions of three restriction fragment length polymorphisms on chromosome 4 relative to known genetic markers.

A library of DNA sequences cloned in lambda phage has been prepared from DNA of chromosomes sorted by cytofluorimetry to give enrichment for chromosome 4. Five sequences have been assigned to chromosome 4 using a panel of hybrid cells, and each has been localised relative to a translocation breakpoint at 4q26. Each of the probes gives a Southern blot pattern which indicates that it does not cross-hybridize with sequences found on other human chromosomes. Three of the probes reveal frequent restriction fragment length polymorphisms (RFLPs) and are useful for linkage analysis.

Chromosome Mapping↗
PubMed1984

The isolation of a genomic clone containing the apolipoprotein CII gene and the detection of linkage disequilibrium between two common DNA polymorphisms around the gene.

We report the isolation of a genomic clone containing the apolipoprotein CII (apo CII) gene and 5' and 3' flanking sequences. A detailed restriction map of the gene has been constructed and DNA fragments that are unique, or low copy number sequences in the genome have been identified. One of these detects a common restriction fragment length polymorphism (RFLP) with the enzyme BglI. Marked linkage disequilibrium is observed between this RFLP and that detected with the apo CII cDNA clone, even though the two variable restriction enzyme sites are approximately 12kb apart. However, the usefulness of the apo CII gene as a marker for linkage studies is increased by the use of both RFLPs.

Alleles↗
PubMed1984

Gene for apolipoprotein CII is on human chromosome 19.

We have used a cloned cDNA probe for human apolipoprotein CII (apo CII) and Southern blotting techniques to identify the human apo CII gene in DNA from a series of rodent X human somatic cell hybrids. Our results provide evidence for the assignment of this gene to human chromosome 19.

Apolipoproteins C↗
PubMed1984

The use of polymorphic DNA and protein markers for the third complement component for determining linkage of familial hypercholesterolaemia.

We have used DNA and protein polymorphisms for the third complement component (C3) to assess the potential of DNA markers in the diagnosis and study of familial hypercholesterolaemia (FH), and to confirm the reported linkage between FH and C3. The inheritance of FH and the C3 gene has been studied in 10 families by combining information from both the protein and DNA polymorphisms. Our results confirm that the C3 gene is loosely linked to the gene causing FH (lod score maximum of 2.0) at a recombination distance of 0.15. When these results are combined with previously published data the overall lod score maximum is 4.75 at a recombination distance of 0.2, meaning that the two genes will be inherited together in only about 80% of children. These results confirm that the gene that causes familial hypercholesterolaemia is linked to C3 and is therefore on chromosome 19, but C3 is not close enough to be used as a diagnostic marker.

Adolescent↗
PubMed1984

Genetic mapping of the human X chromosome by using restriction fragment length polymorphisms.

Using a human X chromosome-specific DNA library, we have found arbitrary single-copy DNA sequences that reveal useful restriction fragment length polymorphisms. The inheritance of these and other available polymorphic DNA markers has been studied in a series of unrelated three-generation families with large sibships. These families reveal parental phase and allow determination of recombination frequencies by counting recombinant and nonrecombinant chromosomes. The resulting genetic map indicates that the minimal distance from Xp22 to Xqter is 215 recombination units. The spacing of the marker loci is such that the majority of the loci on the X chromosome, including disease loci, will lie within 20 centimorgans of at least one of these loci.

Chromosome Mapping↗
PubMed1984

An evaluation of the bacteriolytic and biochemical properties of ceftiolene (42980RP).

Ceftiolene (42980RP) is a new cephalosporin with a broad antibacterial spectrum similar to cefotaxime or ceftriaxone. The characteristics of ceftiolene have been tested in a variety of assays involving various biochemical aspects of the mode of action of beta-lactam antibiotics. The affinities of ceftiolene for penicillin-binding proteins were very comparable with those of ceftriaxone and cefotaxime for Escherichia coli, and generally greater than those of latamoxef (moxalactam) for the higher molecular weight PBPs of E. coli. Enterobacter cloacae. Proteus mirabilis and Pseudomonas aeruginosa. The affinity of ceftiolene for PBP1 of Staphylococcus aureus was greater than those of cefotaxime or latamoxef, but comparable with these antibiotics for PBP3. The bacteriolytic activity of ceftiolene at defined concentrations against Gram-negative organisms was similar to that of ceftriaxone, and significantly better than that of the other third-generation cephalosporins tested. Introduction of plasmid-encoded beta-lactamases into E. coli reduced the wide variation in bacteriolytic effect of the different cephalosporins, and a significant inoculum effect was observed for the bacteriolysis. Chloramphenicol was less antagonistic against ceftiolene- or ceftriaxone-induced lysis than was observed for cefotaxime or latamoxef. Growth of Staph. aureus at low concentrations of ceftiolene caused the bacteria to become more sensitive to lysis by lysostaphin than organisms grown with cefotaxime or latamoxef under the same conditions. These observations confirm the necessity to use techniques other than routine MIC determinations to distinguish between antibiotics which would otherwise appear very similar.

Anti-Bacterial Agents↗
PubMed1984

Development of resistance to beta-lactam antibiotics with special reference to third-generation cephalosporins.

The resistance mechanisms associated with changes in the outer membrane permeability and in beta-lactamase and penicillin-binding-protein production are reviewed. The prevalence of membrane permeability- and chromosome-mediated beta-lactamase-related resistance in Gram-negative bacteria, and of PBP-related resistance in Gram-positive bacteria, with respect to third-generation cephalosporins, is outlined. The frequency of overall resistance to these compounds in two Parisian hospitals during 1983 did not exceed 2% in Enterobacteriaceae but was close to 15% in Pseudomonas sp.

Bacteria↗
PubMed1984

Clinical use of DNA markers linked to the gene for Duchenne muscular dystrophy.

Seventy families with Duchenne muscular dystrophy (DMD) known to the Institute of Child Health fall into three categories with respect to potential linkage analysis with the X chromosome DNA markers RC8 and L1.28 that bridge the DMD gene. Families in which there is at least one obligatory female heterozygote (n = 13). Here 'prediction' and 'exclusion' of DMD gene transmission may be possible, the accuracy being dependent on the closeness of the linkage of the DNA marker(s) to the DMD gene; an illustrative case is reported. Families in which there is a single affected boy, who also has one or more healthy brothers (n = 26). Given an informative restriction fragment length polymorphism (RFLP), the probability that the boy represents a new mutation can be reassessed; it is also possible to 'exclude' the DMD gene in a sister. Families with a single affected boy with no brother (n = 30). Here 'exclusion' of the DMD gene in a sister may be possible. Only in one family was there no possibility of useful linkage analysis. The linkage analysis required is described, and the need to check DMD families for informative RFLPs is stressed.

Base Sequence↗
PubMed1984

The gene for apolipoprotein C-II is closely linked to the gene for apolipo-protein E on chromosome 19.

We have used a common TaqI restriction fragment length polymorphism (RFLP) near the human apolipoprotein C-II (apoC-II) gene to study linkage with apolipoprotein E (apoE). The inheritance of the apoC-II RFLP was followed in seven families that were segregating for apoE protein variants. No recombinants were observed in 20 informative meioses, giving an overall lod score of greater than 4.0 at recombination fraction 0. We have also observed apparent linkage disequilibrium between apoE and the apoC-II RFLP. Taken together these results demonstrate that these two apolipoprotein genes are closely linked and confirm that the gene for apoC-II is on human chromosome 19.

Apolipoprotein C-II↗
PubMed1984

Toward a complete linkage map of the human X chromosome: regional assignment of 16 cloned single-copy DNA sequences employing a panel of somatic cell hybrids.

Closely linked restriction fragment length polymorphisms (RFLPs) are potentially useful as diagnostic markers of genetic defects, and, in principle, RFLPs can be employed to construct a complete linkage map of the human genome. On the X chromosome, linkage studies are particularly rewarding because in man more than 120 X-linked genes are known. Thus, it is probable that each X-specific RFLP will be of use as a genetic marker of one or several X-linked disorders. To facilitate the search for closely linked RFLPs, we have regionally assigned 16 cloned DNA sequences to various portions of the human X chromosome, employing a large panel of somatic cell hybrids. These probes have been used to correlate genetic and physical distances on Xp, and it can be extrapolated from these data that the number and distribution of available Xq sequences will also suffice to span the long arm of the X chromosome.

Animals↗
PubMed1984

The implications of genetic variation in human pathology.

Each human cell contains enough DNA to code for several million proteins. As a result of the technical advances which are broadly described as 'genetic engineering', each of these sequences can be isolated and purified in large amounts, free from those surrounding it in the genome. The sequences are not identical from person to person, nor even for each of a pair of chromosomes for a single person, but contain many variations. These include single base changes in both coding and non-coding regions, deletions, insertions and rearrangements. Using these changes as markers, the molecular geneticist can compare the structure and expression of normal and mutated human gene sequences and follow their inheritance in families.

Cloning, Molecular↗
PubMed1983

Isolation and characterisation of cDNA clones for the A alpha- and gamma-chains of human fibrinogen.

cDNA clones coding for the A alpha- and gamma-chains of human fibrinogen have been isolated from an adult liver cDNA library. Clones were identified by hybridisation with mixtures of synthetic oligonucleotides 17 bases long, predicted using amino acid sequence data for each chain. The cDNA insert sizes are 1,950bp for A alpha-fibrinogen and 950bp for gamma-fibrinogen. The clones do not show any cross-hybridisation. Each cDNA hybridises to a unique sequence in the human genome. In adult human liver, Northern blots give an estimated messenger RNA size of 2.6kb for A alpha-fibrinogen and 1.8kb for gamma-fibrinogen.

Adult↗