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C G Mathew

Publications and source records attributed to C G Mathew.

117 records · Page 7Linked to original sources
PubMed1981

The high mobility group proteins and transcribed nucleosomes.

Monomer nucleosomes released from nuclei during brief micrococcal nuclease digestions are enriched in transcribed sequences (Bloom and Anderson, 1978). These nucleosomes are depleted in H1 and enriched in three high mobility group proteins HMG14, HMG17 and another HMG-like protein. Analysis of such nucleosomes by polyacrylamide gel electrophoresis reveal that they are heterogenous. Similarly, monomer nucleosomes soluble in 0.1 M NaCl separate on polyacrylamide gels into mainly two types of particle, one of which has HMG14 and HMG17 bound. However, the DNA of the HMG-nucleosomes from chick erythrocytes is not enriched in globin sequences, suggesting that protein rearrangement may have occurred.

Animals↗
PubMed1979

Analysis of the high mobility group proteins associated with salt-soluble nucleosomes.

Two methods have recently been described for the isolation of monomer nucleosomes enriched in transcribed sequences which depend on their solubility in 0.1 M NaCl (Levy, W.B. and Dixon (1978), Nucleic Acid Res., 5, 4155-4163) or solutions containing divalent metal ions (Bloom, K.S. and Anderson, J.N. (1978), Cell, 15, 141-150). Using these procedures the proteins associated with such nucleosomes from rabbit thymus, calf liver and hen oviduct nuclei were isolated and analysed. Increased amounts of proteins HMG14 AND HMG17 and small amounts of HMG1 and HMG2 were found associated with the four core histones H2A, H2B, H3 and H4 in these nucleosomes. HMG14 and HMG17 were found to be enriched 2 - 7 fold, suggesting an involvement of these two proteins with transcribed sequences. 0.1 M NaCl-soluble monomer nucleosomes prepared by the method of Levy and Dixon were analysed by polyacrylamide gel electrophoresis and found to be composed of principally two types of particle: 1. Core particles of 145 base pairs of DNA associated with the four core histones only. 2. Nucleosomes with 160 base pairs of DNA associated with the four core histones, increased amounts of HMG14 and 17, and no H1. Small amounts of HMG1 and HMG2 are also detected. These results suggest that HMG14 and HMG17 might be interacting with the 15 base pair linker DNA. A model is presented for the structure of transcriptionally active chromatin.

Animals↗
PubMed1979

Studies on the association of the high mobility group non-histone chromatin proteins with isolated nucleosomes.

Nucleosomes have been isolated from rabbit thymus by sucrose gradient centrifugation, and their high mobility group (HMG) protein content analysed by electrophoresis on polyacrylamide gels. The results suggest that proteins HMG 14 and HMG 17 are associated with the core particle of the nucleosome, and that there are two or more sub-populations of both HMG 1 and HMG 2 molecules. One sub-population appears to be fairly tightly bound to the nucleosome, while another is rapidly released from the chromatin by digestion with micrococcal nuclease. The latter fraction may participate in a higher order folding of the nucleosomes.

Animals↗
PubMedDate not supplied

Deletion of genes on chromosome 1 in endocrine neoplasia.

Recent studies have identified normal cellular DNA sequences which are lost in the development of embryonal and adult tumours. These tumours are thought to arise after a primary mutation in one allele of such a sequence is followed by loss of its normal homologue. In familial cases, the primary mutation is transmitted in the germ line. The secondary mutation may involve a substantial loss of chromosomal material and thus lead to identification of the site of the inherited mutation. We have examined constitutional and tumour genotypes of medullary thyroid carcinomas and phaeochromocytomas which develop in the dominantly inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2) to locate the predisposing gene in this syndrome. We observed deletion of a hypervariable region of DNA on the short arm of chromosome 1 in seven out of fourteen tumours. Analysis of the parental origin of the deleted allele in two families showed that it was derived from the affected parent in one case, which suggests that the deletion does not reflect the site of the inherited mutation in MEN2. The deleted region is distal to the breakpoint commonly detected in neuroblastomas, which share with the tumours of MEN2 embryological origin from neuroectoderm.

Carcinoma↗
PubMedDate not supplied

A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10.

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited cancer syndrome characterized by medullary carcinoma of the thyroid, phaeochromocytoma and hyperparathyroidism. Almost all gene carriers can be detected by screening tests before the age of 40, but the nature and location of the predisposing gene are unknown. Simpson et al. recently reported preliminary evidence for linkage between the DNA probe p9-12A on chromosome 10 and MEN2A. We now report linkage between the MEN2A locus and the interstitial retinol-binding protein gene, which is located on chromosome 10p11.2-q11.2.

Centromere↗
PubMedDate not supplied

Correlation of SMNt and SMNc gene copy number with age of onset and survival in spinal muscular atrophy.

Childhood-onset autosomal recessive spinal muscular atrophy (SMA) is associated with absence of the telomeric survival motor neuron gene (SMNt) in most patients, and deletion of the neuronal apoptosis inhibitory protein (NAIP) gene in the majority of severely affected patients. Analysis of SMNt has been complicated by the existence of a centromeric copy, SMNc, which is almost identical to SMNt but which can be distinguished from it by restriction enzyme analysis. In this study 143 SMA patients have been genotyped for the presence or absence of the SMNt, SMNc and NAIP genes, and the data correlated with quantifiable clinical variables. Although a significant correlation was observed between the presence or absence of the NAIP gene and the severity of the clinical phenotype in SMA patients generally, there was no difference in age of onset or survival in type I patients with the NAIP+ or NAIP- genotype. Fluorimetric PCR analysis of SMNc gene dosage in 57 patients homozygous for the absence of the SMNt gene but in whom the NAIP gene was present showed a highly significant correlation between SMNc copy number and SMA subtype, and between SMNc copy number and both age of onset and length of survival. The data provide strong statistical support for the emerging consensus that the clinical phenotype in SMA is directed primarily by the level of functional SMN protein. The lower SMNc copy number in type I patients in whom the NAIP gene is present suggests that the SMNt gene is removed by deletion in the majority of such patients, rather than by gene conversion as is the case in SMA types II and III.

Age of Onset↗
PubMedDate not supplied

Somatic mosaicism in Fanconi anemia: molecular basis and clinical significance.

Approximately 25% of patients with Fanconi anemia (FA) have evidence of spontaneously occurring mosaicism as manifest by the presence of two subpopulations of lymphocytes, one of which is hypersensitive to cross-linking agents (e.g. mitomycin C) while the other behaves normally in response to these agents. The molecular basis of this phenotypic reversion has not yet been determined. We have investigated 8 FA patients with evidence of mosaicism. Epstein-Barr virus-immortalized lymphoblastoid cell lines established from these patients exhibited an IC50 for mitomycin C of 25 to > 100 nM compared to a mean of 2 +/- 2 nM for 20 nonmosaic FA patients and 49 +/- 11 nM for 8 healthy controls. In 3 patients who were compound heterozygotes for pathogenic FAC gene mutations the molecular mechanism of the mosaicism was investigated by haplotype analysis. The results indicated that an intragenic mitotic recombination must have occurred leading to a segregation of a wild-type allele in the reverted cells and suggested two patterns of recombination. In 1 patient a single intragenic crossover between the maternally and paternally inherited mutations occurred associated with markers located distally to the FAC gene; in the other 2 patients (sibs) the mechanism appears to have been gene conversion resulting in segregants which have lost one pathogenic mutation. In 6 of the 8 patients the hematological symptoms were relatively mild despite an age range of 9-30 years.

Adolescent↗