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R Williamson

Publications and source records attributed to R Williamson.

At least 361 records · Page 20Linked to original sources
PubMed1986

Microdissection of and microcloning from the short arm of human chromosome 2.

A bank of cloned DNA sequences from the distal half of the short arm of human chromosome 2 was generated by using microdissection and microcloning techniques. DNA was purified from 106 chromosomal fragments, manually dissected from peripheral lymphocytes in metaphase, and cloned into the EcoRI site of lambda gt10. A total of 257 putative recombinants were recovered, of which 41% were found to contain human inserts. The mean insert size was 380 base pairs (median size, 83 base pairs), and fewer than 10% of the clones contained highly repetitive sequences. All single-copy sequences examined were shown to map to the short arm of chromosome 2 by using hybrid panels. This technique provides a rapid method of isolating probes specific to a human subchromosomal region to generate linked markers to genetic diseases for which the chromosomal location is known.

Base Sequence↗
PubMed1986

Cystic fibrosis carrier detection using a linked gene probe.

Cloned DNA markers which are closely linked to the gene defect causing cystic fibrosis have recently been described. These markers are sufficiently informative for carrier detection in 80% of families where there is a living cystic fibrosis child and unaffected sibs. The tightly linked DNA marker pJ3.11 was used in this study to identify carriers in six families and exclude carrier status in two subjects. Risk calculations for recessive diseases using linked DNA probes may be complex, but useful information for counselling can be obtained in this way.

Cloning, Molecular↗
PubMed1986

A model system for the analysis of gene exclusion: cystic fibrosis and chromosome 19.

We have used multilocus analysis to exclude the cystic fibrosis locus from six polymorphic DNA markers covering most of chromosome 19. A substantial increase in the confidence for exclusion was obtained using the computer programme LINKAGE compared to analysis of pairwise lod scores. A structured approach to the analysis of linkage to autosomal recessive inherited diseases where the biochemical defect is not known is described.

Child↗
PubMed1986

In utero bladder diversion--problems with patient selection.

Based upon the concept that an obstruction-maldevelopment sequence is reversible after diversion, it has been suggested that the fetus with a bladder outlet obstruction is a potential candidate for in utero intervention. We report an infant who had both renal and pulmonary dysplasia at birth despite a technically successful diversion at 22 weeks' gestation. The poor outcome suggests that the organ damage either occurs so early that it precludes corrective surgery, or that the maldevelopment is not the result of obstruction, but rather a primary mesodermal defect.

Abdomen↗
PubMed1986

Antenatal diagnosis and palliative treatment of nonimmune hydrops fetalis secondary to pulmonary extralobar sequestration.

The causes of nonimmune hydrops fetalis are multiple. Despite the fact that many of the affected fetuses are otherwise free of fatal abnormalities, many die in the neonatal period from pulmonary hypoplasia. The overall perinatal mortality is as high as 80%. Extralobar pulmonary sequestration is an abnormal and nonaerated mass of extra pulmonary-located lung tissue supplied by a systemic artery, and is a rare cause of nonimmune hydrops. In the only two published reports, the hydropic fetuses died at birth. Both the first antenatal diagnosis of this disorder and the first attempt at palliative in utero therapy are reported herein. Though the fetus ultimately delivered prematurely and succumbed, treatment was associated with both subjective improvements in fetal well-being and objective reversal of the hydrops.

Adult↗
PubMed1986

Towards a complete linkage map of the human X chromosome.

In the seven years since the first human gene was cloned, several hundred coding sequences and many more random single copy DNA sequences have been isolated. Many of these show restriction fragment length polymorphisms (RFLPs) and can be used as genetic markers in inheritance studies. RFLPs enable the construction of complete linkage maps of individual human chromosomes which can then be used as a mapping resource for other genes and disease loci. The isolation of chromosome specific sequences has been greatly facilitated by the purification of human chromosomes by flow cytometry. Sub-localisation of the polymorphic DNA probes along the chromosome can be achieved using in situ hybridisation or rodent/human hybrid cell lines. There are now more than one hundred DNA probes assigned to the human X chromosome and a preliminary genetic map suggests that the chromosome is at least 200 cm long. Some of these DNA sequences have been shown to be linked to disease loci such as Duchenne and Becker muscular dystrophy, X-linked mental retardation and retinitis pigmentosa.

Cell Fractionation↗
PubMed1986

The analysis of multiple polymorphic loci on a single human chromosome to exclude linkage to inherited disease: cystic fibrosis and chromosome 4.

Classical linkage programs analyze the segregation of two markers in informative families. When several markers are available for one human chromosome, pairwise analysis can exclude linkage between each marker and an inherited disease. The identification of restriction fragment length polymorphisms has made many new informative markers, assigned to chromosomes, available. We have adapted the multipoint linkage program MLINK developed by Lathrop et al. in order to exclude linkage between cystic fibrosis and several markers known to be on human chromosome 4. The exclusion obtained is greater than that for a pairwise analysis.

Chromosome Mapping↗
PubMed1986

Exclusion of human chromosome 13q34 as the site of the cystic fibrosis mutation.

We have studied a family in which both cystic fibrosis (CF) and an unbalanced translocation between chromosomes 6 and 13 are found. As CF occurs in the child who is effectively monosomic for the translocated part of the long arm of chromosome 13, it was suggested that the locus of the gene mutation causing CF is on chromosome 13q34. The gene for human coagulation factor X is located at 13q34, and we have found a restriction fragment length polymorphism (RFLP) that is revealed by a cloned cDNA coding for this protein. Linkage analysis in eight CF families shows no evidence of cosegregation between CF and the gene for factor X, strongly suggesting that the locus for the defect causing cystic fibrosis is not at 13q34.

Chromosome Mapping↗
PubMed1986

Screening for genetic diseases with molecular probes.

Over 500 human genes have now been cloned. The study of many of these has greatly improved our knowledge of the causes of certain genetic diseases, and our ability to diagnose them. The linkage of random polymorphic DNA probes has also aided the mapping of disease loci, and the diagnosis of human pathology. In some cases linkage may prove to be the starting point for the isolation of genes causing disease where the biochemical defect is not characterised. This review looks at the impact of recombinant DNA technology on the study of human genetic disease.

Chromosome Deletion↗
PubMed1985

A selective N-methyl-D-aspartate antagonist depresses epileptiform activity in rat hippocampal slices.

The sensitivity of convulsant-induced epileptiform activity in the hippocampus to the selective N-methyl-D-aspartate (NMDA) antagonist D-2-amino-5-phosphonovalerate (D-APV) was examined using in vitro electrophysiological techniques. This compound reduced the number and size of the synaptically evoked population spikes recorded in the CA1 region in the presence of the convulsants, pentylenetetrazol, bicuculline or folate. Intracellular recordings in the presence of bicuculline showed that D-APV reduced the late component of the excitatory postsynaptic potential and the number of action potentials evoked synaptically. A mechanism is suggested to explain how NMDA receptors, which are known not to be involved in normal synaptic transmission in hippocampal slices, can contribute to epileptiform activity.

2-Amino-5-phosphonovalerate↗
PubMed1985

Inhibition of cell wall synthesis and acylation of the penicillin binding proteins during prolonged exposure of growing Streptococcus pneumoniae to benzylpenicillin.

Growing cultures of an autolysis-defective pneumococcal mutant were exposed to [3H]benzylpenicillin at various multiples of the minimal inhibitory concentration and incubated until the growth of the cultures was halted. During the process of growth inhibition, we determined the rates and degree of acylation of the five penicillin-binding proteins (PBPs) and the rates of peptidoglycan incorporation, protein synthesis, and turbidity increase. The time required for the onset of the inhibitory effects of benzylpenicillin was inversely related to the concentration of the antibiotic, and inhibition of peptidoglycan incorporation always preceded inhibition of protein synthesis and growth. When cultures first started to show the onset of growth inhibition, the same characteristic fraction of each PBP was in the acylated form in all cases, irrespective of the antibiotic concentration. Apparently, saturation of one or more PBPs with the antibiotic beyond these threshold levels is needed to bring about interference with normal peptidoglycan production and cellular growth. Although it was not possible to correlate the inhibition of cell wall synthesis or cell growth with the degree of acylation (percentage saturation) of any single PBP, there was a correlation between the amount of peptidoglycan synthesized and the actual amount of PBP 2b that was not acylated. In cultures exposed to benzylpenicillin concentrations greater than eight times the minimal inhibitory concentration, the rates of peptidoglycan incorporation underwent a rapid decline when bacterial growth stopped. However, in cultures exposed to lower concentrations of benzylpenicillin (one to six times the minimal inhibitory concentration) peptidoglycan synthesis continued at constant rate for prolonged periods, after the turbidity had ceased to increase. We conclude that inhibition of bacterial growth does not require a complete inhibition or even a major decline in the rate of peptidoglycan incorporation. Rather, inhibition of growth must be caused by an as yet undefined process that stops cell division when the rate of incorporation of peptidoglycan (or synthesis of protein) falls below a critical value.

Acylation↗
PubMed1985

A common DNA polymorphism of the low-density lipoprotein (LDL) receptor gene and its use in diagnosis.

A cloned gene probe coding for the low-density lipoprotein (LDL) receptor was used to detect a restriction fragment length polymorphism with the enzyme Pvu II. The frequency of the rare allele is approximately 0.2 both in normal controls and individuals with familial hypercholesterolaemia (FH). About 30% of individuals are heterozygous for the polymorphism, and are potentially informative for family studies and for early diagnosis of FH. This polymorphism was used to follow the inheritance of the LDL receptor gene in two families with FH. In these families, the polymorphism co-segregates with the disease unambiguously, and therefore can be used for early diagnosis.

Alleles↗