Baptista, Pedro M.R.V.; (2000) Integrated mapping and gene analysis in regions showing loss of heterozygosity in human breast cancer in the short arm of Chromosome 1. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

A flow-sorted chromosome 1 cosmid library was used to produce a cosmid pocket map spanning two regions in chromosome 1p - approximately 10 Mb in 1p31.1 and 1.7 Mb in 1p13.1. Loss of heterozygosity (LOH) in human breast cancer has been described at these regions. In chromosome 1p13.1 a more detailed physical map consisting of overlapping genomic inserts contained within bacterial recombinant clones was constructed. To the present moment no genomic sequence is yet available at this chromosomal region. For the identification of novel genes, exon trapping and cDNA selection were performed, on 9 overlapping clones from the physical map. The resulting putative exons/transcripts were analysed and compared with non-redundant, cDNA and protein databases. The DNA sequence of seven clones was identical to human cDNA clones. Two highly significant similarities of translations of these clones were found with a human alpha-mannosidase and a rat prostaglandin associated regulatory protein. Both genes were located in a smallest region of overlapping deletion in tumour DNA from patients with breast cancer. Analysis of the coding sequence of the genes using genomic DNA from patients with breast cancer showing LOH at this region will be presented in the thesis.

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