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Title: Radiation hybrid mapping of genes in human and baboon
Author: Hayes, P. D.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1998
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This thesis investigates the use of whole-genome radiation hybrid (WG-RH) mapping for the creation of a gene map of the human genome, and comparative maps of primate genomes. A collection of human expressed sequence tags (ESTs) was examined for sequences that could serve as gene-based markers. The ESTs were assigned to chromosomes by monochromosomal somatic cell hybrid mapping. ESTs on every chromosome were then localised relative to a framework of 408 markers of known position on the human genetic map, by two-point and multipoint maximum likelihood analysis of their segregation in a panel of 168 human WG-RH clones. Additional ESTs were mapped with a re-grown 93-clone subset of the WG-RH panel, which was also used by a consortium of laboratories for large-scale mapping of ESTs. Comparison with their results supports the mapping results obtained for matching ESTs. To develop markers for comparative WG-RH mapping, published human STSs from chromosome 22 (HSA22) were tested with baboon and hamster DNA: suitable PCR conditions were found for 118 (39%) of 278 STSs. The patterns of retention of 93 of these markers were determined in a panel of 144 baboon (Papio hamadryas) WG-RH clones created by Dominique Spillett, who also provided retention data for a further 26 markers. Two-point analysis of the combined data shows that all 119 HSA22 markers are also linked in the baboon with at least lod 3 statistical support, and 97 markers have at least lod 6 support for linkage. This is consistent with published cytogenetic data that identifies the HSA22 homologue as one arm of baboon chromosome 13. Markers were ordered by maximum likelihood analysis, building on a framework of 19 markers supported to lod 4: the final map contains 96 markers, of which 53 are ordered with at least lod 3 support. The map extends from the most centromeric marker on the Genethon human genetic map to a subtelomeric marker. Comparison with the published human maps shows complete or near-complete conservation of linkage.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available