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Title: Computational analysis of a candidate region for psychosis
Author: Ballereau, Stéphane
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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The aim of this thesis was to develop and use bioinformatic tools to direct laboratory work on a candidate region for BPAD and schizophrenia on the short arm of human chromosome 4. Specifically, the research aimed to facilitate the management and analysis of data generated by allelic association studies, and identify putative functional sequences as targets for SNP selection. This thesis first reports the creation of an extension of the ACeDB database used by the laboratory to manage the sequence of the candidate region, and a front-end to manage and analyse raw data generated by allelic association studies based on individual genotypes and pooled DNA. It then describes various strategies to define putative non-coding functional sequences benchmarked against a set of genes with experimentally verified regulatory regions. Initially, methods for detecting known transcription factor binding sites and novel motifs were combined with tests of sequence conservation between human and mouse. This approach showed modest sensitivity and generated a high rate of false positives. Next, a purely comparative genomics approach was explored using publicly available genome sequences from human, mouse, rat, chicken, zebrafish and pufferfish. Several scoring systems for multiple alignments of genomic sequences were tested. The most successful scoring scheme detected regulatory sequences in 78% of the control genes using human, mouse and rat sequences. Predictions of the functional potential of non-coding DNA were sufficiently sensitive and specific to suggest a limited number of putative functional regions for experimental verification. This approach was therefore applied to genes in the 4p region linked to psychosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available