PubMed Health⌕ Search

Biomedical subjects

W Brammar

Publications and source records attributed to W Brammar.

4 recordsLinked to original sources

Allelic imbalance on chromosome 1 in human breast cancer. I. Minisatellite and RFLP analysis.

In order to characterise the role of chromosome 1 more fully in breast cancer, polymorphic markers mapping along the length of the whole chromosome were used to assess a panel of 71 tumour-lymphocyte pairs for allelic imbalance. Complex patterns of alterations were established that are consistent with cytogenetic data in the literature. Deletion mapping of individuals with loss of heterozygosity identified five independent smallest common regions of deletion, two of which are novel. There are also three discrete regions showing a gain in copy number of one homologue. The two arms of the chromosome may be subject to different events; the short arm primarily undergoes interstitial deletions, whereas the long arm is subject to whole arm events (as both gains and losses) as well as regional deletions.

Alleles↗

Loss of heterozygosity on the X chromosome in human breast cancer.

The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.

Alleles↗

Confirmation of the copy number of chromosome 1 in interphase nuclei from paraffin sections of breast tumours by fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) was used to establish the copy number of chromosome 1 in a set of nine breast tumours in which the chromosome had previously been shown to have undergone a variety of rearrangements by loss of heterozygosity studies. In each case, FISH with satellite III DNA from chromosome 1q12 confirmed the results obtained by Southern hybridization. Importantly, in all five cases with rearrangements thought not to involve the centromeric region, FISH showed that the events had not disrupted the gross chromosome structure. This study highlights the potential of using the two techniques together to obtain a clearer picture of both large- and small-scale alterations to chromosomes in solid tumours.

Alleles↗

Efficient repression by a heterodimeric repressor in Escherichia coli.

Previous studies with purified variants of the 434 repressor having different operator-binding specificities have demonstrated the interactions of a heterodimeric repressor with a hybrid operator site. The present study investigates the interactions between the 434 repressor and its operator site. The optimum 434 operator half-site is used with a P22 operator half-site to create a hybrid 434/P22 operator. We show that this hybrid operator can be efficiently bound by a heterodimeric repressor, consisting of one wild-type 434 repressor monomer and one 434 repressor monomer with the binding specificity of the P22 repressor, to bring about repression in Escherichia coli.

Amino Acid Sequence↗