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Expression quantitative trait loci in human brain tissues

Gibbs, JR; (2016) Expression quantitative trait loci in human brain tissues. Doctoral thesis , UCL (University College London). Green open access


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To what extent genetic variability influences gene expression in human primary tissues is a critical question in molecular genetics. Work investigating this phenomenon is not only interesting biologically, but also has the potential to provide mechanistic insight into traits, including disease. The past decade has seen tremendous progress in this field, and this thesis includes a description of work that spanned from the relatively early stages of this type of work, to current, more refined efforts. This work sought to ask three questions: first, are eQTL detectable in brain tissues using whole genome methods; second, are eQTL measurably different in different parts of the brain; and third, does the investigation of eQTL in a particular neuronal cell type offer significant advantages over similar studies in tissue with a mixed cellular composition. In the first part of this work, I present a pilot study aimed at assessing the feasibility of eQTL detection in brain tissue. This study showed that the use of genome wide genotyping and expression arrays revealed a number of significant eQTL, and that in general, when genetic variability was associated with expression, the genetic locus and the expressed transcript were physically close. This work was then expanded to assess eQTL in multiple brain regions, with an attempt to assess whether eQTL were measurably different between distinct brain regions. In this work, tissue from cerebral frontal cortex, cerebral temporal cortex, caudal pons, and cerebellum was used. The analysis showed that there are region-specific eQTL, but that many of the strongest eQTL were present in multiple tissues. Lastly, I show using data from laser capture microdissected Purkinje cells that additional cell-type specific eQTL may be found that are not revealed when performing eQTL in heterogeneous tissue containing this cell type. In summary this work initially revealed the feasibility of eQTL work in human brain, showed that eQTL were measurably different, but generally similar across varied brain tissues, and showed that there are likely several advantages in pursuing single cell type work in tandem with whole tissue efforts.

Type: Thesis (Doctoral)
Title: Expression quantitative trait loci in human brain tissues
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Third party copyright material has been removed from ethesis.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
URI: https://discovery.ucl.ac.uk/id/eprint/1496882
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