Use this URL to cite or link to this record in EThOS:
Title: An analysis of transcript variation in human Xp11.23
Author: Eades, T. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2005
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
This thesis describes an analysis of the genome features and gene content in human Xp11.22-p11.3. Human Xp11.23 has the highest density of genes in the human X chromosome, and this analysis identified 77 known and 11 novel genes. The pseudogene content of this region was also high – it contained 59 processed and 7 non-processed pseudogenes. More detailed investigation of these revealed that the number and diversity of gene products generated from genes within Xp11-23 greatly exceeded the number of coding regions that it contained. In order to further study the impact of alternative splicing in Xp11-23 detailed analysis was completed on 18 genes using bioinformatics and comparative analysis together with a targeted RT-PCR sequencing strategy. This analysis identified more than 120 transcripts variants. Preliminary tissue profiling of these transcripts was completed using RT-PCR. The functional consequences of alternative splicing were then investigated for one gene, polyglutamine binding protein 1, PQBP1. This ubiquitously expressed gene has been associated with various disease phenotypes including X-linked mental retardation. Renpenning syndrome and other neurodegenerative disorders. In concert with expression and evolutionary analysis, a cloned open reading frame collection was generated, for 16 transcript variants. The relative abundance of minor transcript variants was determined in a panel of 20 human tissues where it was found that together the minor variants accounted for less than 10% of the all PQBP1 transcripts. Following in silico analysis of the predicted protein sequences, it was found that transcript variation was associated with variable inclusion of a nuclear localisation signal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available