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Title: Physical mapping and identification of genes from a region of chromosome 11 adjacent to a translocation breakpoint associated with schizophrenia
Author: Devon, Rebecca S.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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Schizophrenia is the most severe of all the psychoses, affecting approximately 1% of the world's population. Evidence accumulated from numerous family, twin and adoption studies has firmly established a significant genetic component. The densely spaced markers now available throughout much of the human genome have facilitated whole genome positional cloning efforts. However the presence of a cytogenetic rearrangement associated with the disorder, such as the balanced t(1;11) translocation described here, provides an extremely valuable research tool. Generation and mapping of markers in the region of this translocation led to the construction of a 3Mb yeast artificial chromosome (YAC) contig across the chromosome 11 breakpoint. This thesis begins with the isolation of YAC end clones by 'splinkerette PCR', an improved alternative to vectorette PCR, which facilitated the contig construction. A search for foetal brain-expressed genes from this YAC was then undertaken, using two complementary methods of cDNA selection, ('hybrid fishing' and 'end ligation' coincidence sequence cloning). A thorough analysis of the product library and confirmatory hybridisation to the YAC and cDNA led to the identification of an additional member of the α-tubulin gene family, and several novel gene fragments, comprising at least two genes. Extensive sequence and expression analysis of the α-tubulin gene suggest that it is a processed psuedogene, although its potential as a candidate gene for psychiatric illness in this family cannot be discounted. The novel gene fragments have been mapped relative to each other and to rare cutter restriction sites in cloned genomic DNA, allowing one group of four fragments to be tentatively assigned to a single CpG island-associated gene. These can now be tested as genetic susceptibility factors in schizophrenia.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available