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Title: Mapping and mutational analysis of chromosome 11q12-13
Author: Coyle, Elizabeth
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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This thesis describes a) the isolation and mapping of new markers from human chromosome 11q12-13 and b) the mutational analysis of a gene from this region as a candidate for an inherited deafness syndrome. A number of markers were concentrated in a sub region of 11q13 which had been linked to several important disorders, and these were used to isolate YACs. Thus the formation of a cloned DNA map of the region was initiated. In parallel I examined the Olfactory Marker Protein (OMP) gene as a candidate for Usher Syndrome Type IB, by DNA sequencing and mutational analysis of affected individuals. Usher syndrome is characterised by deafness and retinitis pigmentosa. In Type I, vestibular dysfunction is also a feature of the disorder. The disorder is genetically heterogeneous and for each subtype several genetic loci have been linked in individual populations: Type IB has been linked to 11q13. A stereociliary defect was proposed, and the mapping of OMP to the linked region, its expression in olfactory nasal cilia and the CNS, and the mapping of the mouse OMP gene to the synthetic region on mouse chromosome 7 very close to Shaker-1, a possible mouse homologue of Usher syndrome type I, justified close examination of OMP as a candidate for both disorders. A human genomic clone was therefore obtained and sequenced, several different methods of mutation detection compared, and the value of the chemical mismatch cleavage technique demonstrated. At the same time, comparative mapping was carried out by mapping candidates from the Shaker-1 nonrecombinant region on the somatic cell hybrid panel. Variants of the OMP gene were identified, but were formally excluded as candidates when a gene located very close to OMP was shown by others to be mutated in Shaker-1 mice and USHIB patients.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available