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Physical mapping and identification of novel genes in human chromosome 21q11

Groet, Jürgen; (1999) Physical mapping and identification of novel genes in human chromosome 21q11. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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A physical map, of approximately 3.2 Mbp, consisting of overlapping genomic inserts contained within bacterial recombinant clones was constructed in the qll region of human chromosome 21. This region has been associated with Alzheimer's disease, non-small cell lung carcinoma (NSCLC) and a specific form of acute non-lymphocytic leukaemia. Exon trapping was performed, for the identification of novel genes, on twenty-two overlapping clones from the physical map. Ninety-three different species of putative exons were analysed and compared with non-redundant, cDNA and protein databases. The DNA sequence of nineteen exon trapped clones was identical to human cDNA clones. The most significant similarities of translations of the exon trapped products were found with a rat lipase, a human multi-drug resistance protein and a ubiquitin carboxyl-terminal hydrolase from C. elegans. Analysis of overlapping cDNA clones, exon trapped material and products from rapid amplification of cDNA ends, led to the identification of two novel genes. The first gene (3803 bp. 1055 amino acids), which was located in a smallest region of overlapping deletion in tumour DNA from patients with NSCLC, showed very high similarity lo ubiquitin-specific proteases. This function was studied by an in vitro assay, which showed de-ubiquitination of a model fusion protein by the protein product of the novel gene. Sequencing of exons from this gene using genomic tumour DNA from patients with NSCLC and late onset Alzheimer's disease did not show any mutations. The second gene (1888 bp. 373 amino acids) showed similarity to the protein products of novel putative genes located on chromosomes Xq25-26.1 and 6q22.3. The function of this protein is unknown. Analysis of the coding sequence of the gene using genomic DNA from patients with NSCLC, familial early onset Alzheimer's disease, late onset Alzheimer's disease and from Down syndrome patients with acute non-lymphocytic leukaemia failed to show any mutations.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Physical mapping and identification of novel genes in human chromosome 21q11
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10110845
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