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Title: Molecular genetic analysis of chromosome 11q13 : localisation of the multiple endocrine neoplasia type 1 gene
Author: Pang, Joanna Theresa
ISNI:       0000 0001 3466 5498
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1996
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Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pituitary and pancreas. The MEN1 tumour suppressor gene has been localised to chromosome 11q13, and the main aspect of this thesis involved the construction of a detailed genetic map of the region. This not only helped to further localize the MEN1 gene, but also contributed to the overall genetic map of 11q13 which will facilitate positional cloning studies of other disease genes mapping to this region. The three parallel mapping strategies which were adopted were hybrid mapping, linkage studies and tumour deletion mapping. A panel of 12 hybrids was used to map 16 polymorphic loci, 20 non-polymorphic loci and 35 cosmids to different regions within 11q13. The 16 polymorphic loci were subsequently employed m linkage studies of 33 MEN1 families with a total of 600 members (134 affected). Tumour deletion mapping studies were also performed on 94 MEN1-associated tumours, and the combined results of these three mapping studies established the order of 21 loci. Linkage studies localised the MEN1 gene to a 3.8 cM interval flanked by the loci PYGM and D11S97, and tumour deletion mapping studies further mapped the MEN1 gene to a 2.4 cM interval between SEA and D11S97. In addition, the linkage studies identified five loci which were non-recombinant m affected individuals. These were used to define the disease haplotype and identify mutant gene carriers for investigating the age-related penetrance of the disorder. Additional positional cloning studies aimed at identifying the MEN1 gene, were also undertaken. These involved the mapping of an 11q13 breakpoint m a patient with lipomata by fluorescence in situ hybridisation, the analysis of three candidate genes, CAPN1, ZFM1 and PLC3, for abnormalites in 68 unrelated MEN1 patients, and the isolation and characterisation of three YAC clones identified with one of these candidates.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Genetics