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Biomedical subjects

S J Knight

Publications and source records attributed to S J Knight.

48 records · Page 3Linked to original sources
PubMed1991

The physical map of chromosome arm 19q: some new assignments, confirmations and re-assessments.

We have constructed and analysed somatic cell hybrids from cell lines containing balanced reciprocal translocations involving chromosome 19 and providing two new breakpoints on 19q. These and other hybrids have been tested with a series of markers from 19q to enhance the existing map. Several new cloned DNA sequences that map to 19q13.3-19qter are reported; the locus D19Z1 has been analysed by CHEF gel electrophoresis.

Animals↗
PubMed1991

Genotype prediction in the fragile X syndrome.

Fragile X positive, mentally retarded males have been shown to have an insertion or amplification of DNA sequences at, or close to, the site of expression of the fragile site. We show here the application of the detection of such changes to the diagnosis of affected males and female carriers and the identification of normal transmitting males. One fragile X negative male with the clinical features of the Martin-Bell syndrome also possesses an inserted/amplified DNA sequence. The implications of these results for screening for the fragile X syndrome are discussed.

Blotting, Southern↗
PubMed1991

Assignment of Emery-Dreifuss muscular dystrophy to the distal region of Xq28: the results of a collaborative study.

Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked humeroperoneal dystrophy associated with cardiomyopathy that is distinct from the Duchenne and Becker forms of X-linked muscular dystrophy. Linkage analysis has assigned EDMD to the terminal region of the human X chromosome long arm. We report here further linkage analysis in two multigenerational EDMD families using seven Xq28 marker loci. Cumulative lod scores suggest that EDMD is approximately 2 cM from DXS52 (lod = 15.67) and very close to the factor VIII (F8C) and the red/green color pigment (R/GCP) loci, with respective lod scores of 9.62 and 10.77, without a single recombinant. Several recombinations between EDMD and three proximal Xq28 markers suggest that the EDMD gene is located in distal Xq28. Multipoint linkage analysis indicates that the odds are 2,000:1 that EDMD lies distal to DXS305. These data substantially refine the ability to perform accurate carrier detection, prenatal diagnosis, and the presymptomatic diagnosis of at-risk males for EDMD by linkage analysis. The positioning of the EDMD locus close to the loci for F8C and R/GCP will assist in future efforts to identify and isolate the disease gene.

Chromosome Mapping↗
PubMed1990

Isolation of the human chromosomal band Xq28 within somatic cell hybrids by fragile X site breakage.

The chromosomal fragile-site mapping to Xq27.3 is associated with a frequent form of mental retardation and is prone to breakage after induced deoxyribonucleotide pool perturbation. The human hypoxanthine phosphoribosyltransferase (HPRT) and glucose-6-phosphate dehydrogenase (G6PD) genes flank the fragile X chromosome site and can be used to monitor integrity of the site in human-hamster somatic cell hybrids deficient in the rodent forms of these activities. After induction of the fragile X site, negative selection for HPRT and positive enrichment for G6PD resulted in 31 independent colonies of HPRT-,G6PD+ phenotype. Southern blot analysis demonstrated the loss of all tested markers proximal to the fragile X site with retention of all tested human Xq28 loci in a majority of the hybrids. In situ hybridization with a human-specific probe demonstrated the translocation of a small amount of human DNA to rodent chromosomes in these hybrids, suggesting chromosome breakage at the fragile X site and the subsequent translocation of Xq28. Southern blot hybridization of hybrid-cell DNA, resolved by pulsed-field gel electrophoresis, for human-specific repetitive sequences revealed abundant CpG-islands within Xq28, consistent with its known gene density. The electrophoretic banding patterns of human DNA among the hybrids were remarkably consistent, suggesting that fragile X site breakage is limited to a relatively small region in Xq27-28. These somatic cell hybrids, containing Xq27.3-qter as the sole human DNA, will aid the search for DNA associated with the fragile X site and will augment the high resolution genomic analysis of Xq28, including the identification of candidate genes for genetic-disease loci mapping to this region.

Animals↗
PubMed1990

Industrial employee drug screening: a blind study of laboratory performance using commercially prepared controls.

Reference laboratories are an integral component of any industrial employee drug screening program. We evaluated the performance and accuracy of the reference laboratories used by Rockwell International, a large industrial employer with an active drug screening program. A total of 829 commercially prepared control samples containing drugs of abuse, over-the-counter drugs, and analytes found in the normal employee population were disguised as routine submissions to reference laboratories used by nine Rockwell facilities. Analyses of results included compilation of false-positive and false-negative errors per drug per laboratory and a correlation of errors with preliminary and confirmation methods. Error rates of 2% false-positive results and 20% false-negative results were found for all laboratories. The errors were not limited to any one technique nor to any particular drug. The error rates observed suggest the need for routine blind testing programs and increased interaction between industry and laboratories.

Animals↗
PubMedDate not supplied

Body, mind and spirit: towards the integration of religiosity and spirituality in cancer quality of life research.

The importance of religion and spirituality to the American public has been highlighted by recent opinion polls, media attention and empirical studies. Psychosocial researchers are incorporating these variables into studies of emotional and physical illness. A number of studies have found that, for cancer patients, religious, spiritual and quality of life concerns are paramount. This paper reviews the literature relating religion and spirituality to physical and emotional health and quality of life. Definitions and measurement issues related to religiosity/spirituality and quality of life are discussed. The paper provides a rationale and methodological suggestions for future studies assessing religious and spiritual beliefs of cancer patients in relation to quality of life. The authors conclude that regular inclusion of religiosity and spirituality measures in quality of life studies is needed in order to understand the integration of mind, body and spirit in cancer care.

Humans↗
PubMedDate not supplied

Molecular studies of the fragile X syndrome.

We have studied families segregating for the fragile X syndrome for the presence of amplification of the CGG repeat sequence adjacent to the HpaII Tiny Fragment (HTF) island in the FMR-1 gene. We demonstrate that 138/143 fragile X positive, mentally retarded males show a characteristic smear of fragments corresponding to somatic variation in the amplification of the CGG sequence. In 7/8 normal transmitting males (NTM's), we show that there is a small amplification of sequence but no evidence for somatic variation. Defined mutated fragments in the size range found in NTM's are seen in daughters of NTM's. The daughters of these female carriers show either a defined fragment in the NTM size range, a defined larger fragment or a heterogeneous pattern of fragments. In the latter 2 cases the clinical phenotype of the females cannot easily be predicted, presumably because of variable X inactivation. In some families, the observed DNA genotype does not correlate with the phenotype; in others we demonstrate the occurrence of individuals with a mosaic DNA genotype. The implications of these data for diagnosis of the disease are discussed.

DNA Mutational Analysis↗
PubMedDate not supplied

Molecular analysis of the fragile X syndrome.

Carriers of the fragile X mutation possess more than the normal number of copies of a trinucleotide repeat (CGG) within the coding region of a gene designated as FMR-1 in Xq27. The clinical phenotype is determined by the number of copies of the CGG repeat. DNA-based methods for the detection of the fragile X mutation are now available which greatly assist in the genetic diagnosis of this disorder. Direct detection of the mutation enables the identification of fragile X negative normal transmitting males and fragile X negative carrier females.

Fragile X Messenger Ribonucleoprotein 1↗
PubMedDate not supplied

Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres.

We report an innovative fluorescence in situ hybridization technique which exploits a unique resource of 41 telomere-specific probes and allows the simultaneous analysis of the subtelomeric region of every chromosome for deletion, triplication and balanced translocation events. This technique requires only a single microscope slide per patient and is expected to be a useful diagnostic tool with applications in the fields of idiopathic mental retardation, the detection of congenital abnormalities and in some forms of cancer. This will lead to more accurate genetic counselling of patients and their families and will provide the basis for future diagnostic, therapeutic and preventative measures.

Chromosome Aberrations↗