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Title: Immunoglobulin superfamily proteins in human and mouse
Author: de Bono, B.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2004
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Automated gene-prediction procedures have a number of shortcomings, and a method has been developed to address some of these. My approach drew upon the ability of hidden Markov models to detect distantly-matching patterns of IgSF sequences at both transcript and genomic DNA level. Ensembl gene predictions were used to locate the majority of human and mouse genes, but my method also detected IgSF genes just out of reach of standard pairwise techniques, resulting in a significantly improved coverage of IgSF genome coding sites. The experimental characterisation of two novel non-classical MHC mouse genes was carried out by a collaborating group. In total, the IgSF numbers 893 genes in human and 758 genes in mouse. This description of the IgSF domain across two distinct species allows us to chart the conservation and diversification process that occurs in a functionally important superfamily. The human-mouse common ancestor possessed at least 315 IgSF genes and, subsequent to divergence, a further 43 genes in mouse and 61 genes in human have been created by duplication. Six antibody and six TCR segment libraries in human, mouse and rat, were also annotated. These provide a similar function in both organisms, and are located in a single, well-circumscribed region of the genome. Comparative structural analysis of the repertoire of functional segments of the human and mouse VH locus was also carried out. Although the mouse repertoire (92 functional VH segments) is twice the size of the human set, the main families/groups of VH sequences and the canonical structure combinations are conserved. 70% of the human sequences and 97% of the mouse sequences therefore belong to an equivalent family/group and also have the same canonical structure combination. Phylogenetic analysis revealed that these sequences have arisen subsequent to the divergence of the mouse and human from their common ancestor.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available