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A molecular genetic analysis of human chromosome 13

Hawthorn, Lesley Ann; (1995) A molecular genetic analysis of human chromosome 13. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Chromosome 13 translocations with breakpoints in 13q14 are frequently seen as the only karyotypic abnormality in B-cell chronic lymphocytic leukaemia (BCLL). Somatic cell hybrids were generated which contained both reciprocal partners of these translocations. In all cases small deletions were found at the translocation site suggesting the involvement of a tumour suppressor gene in BCLL leukaemogenesis. The genetic map in this region was shown to be RB1-MGG15-D13S25-D13S31- D13S59. The smallest region of overlap of the BCLL deletions was between RB1 and D13S31. Loss of heterozygosity studies in BCLL showed that allele loss was centered around the 1 Mbp MGG15-D13S25 interval. To increase the number of markers in this region the Genethon microsatellite linkage map for chromosome 13 was integrated with the physical map of the chromosome using a panel of somatic cell hybrids. Only two new markers were assigned to the smallest BCLL deletion. These markers, together with MGG15 and D13S25, were used to construct a YAC contig across the smallest deletion using vectorette end-rescue walking. All YACs were shown to be unrearranged using fluorescence in situ hybridisation (FISH). These YACs were used to probe a chromosome 13-specific cosmid library to isolate clones from the BCLL deletion region. Exon-trapping was then attempted using these cosmids but no transcribed sequences could be detected. During the course of this thesis a series of expressed sequence tags (ESTs), corresponding to genes, were mapped using the regional mapping panel. Although none of the ESTs mapped to the BCLL YAC contig, several mapped to parts of the chromosome containing genes responsible for human genetic diseases. Two of these clones mapped to the 13q13 region shown to contain the breast cancer 2 (BRCA2) gene and are being pursued as candidates. The genetic resources characterised in this thesis are being used in the Human Genome Mapping project to improve the physical map of chromosome 13 as well as identifying candidate genes for a variety of hereditary diseases.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: A molecular genetic analysis of human chromosome 13
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; B-cell chronic lymphocytic leukemia
URI: https://discovery.ucl.ac.uk/id/eprint/10103178
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