|Title:||Identifying Novel Genes and Variants in Eye Diseases|
|Authors:||Ng, Wan Yi|
|Publisher:||University of Sydney.|
Children's Medical Research Institute.
Children's Hospital at Westmead Clinical School.
|Abstract:||The overall aim of this project is to analyse patients and families with congenital ocular disorders of unknown genetic aetiology, using the most appropriate molecular and genomic approaches in novel candidate gene and variant identification. The first aim uses a candidate gene approach to analyse a family of two sibships with deceased offspring diagnosed with Fraser Syndrome and microphthalmia syndrome 9, two different rare syndrome disorders with overlapping clinical features. This resulted in the identification of novel FRAS1 and STRA6 mutations, genes known to be associated with Fraser syndrome and microphthalmia syndrome 9, respectively. The second aim identified a candidate retinitis pigmentosa (RP) gene in a patient with a paracentric 15q inversion. Using various techniques – karyotype analysis, FISH, paired-end diTag next generation sequencing – a novel RP gene was identified close to the first breakpoint. Knockout mice exhibit motor learning deficit, similar to that noted in our patient. Collaborative results suggest an additional impact on visual function. The third aim investigates affected offspring in six families diagnosed with a novel form of congenital disorder of glycosylation. A linkage approach identified several possible candidate disease genes, including one of particular significance. No convincing exonic pathogenic variants were identified in this aim, and further studies are planned including whole genome sequencing to detect structural or other variants in the candidate disease genes, that are not easily detected with current molecular techniques.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|NG Wan Yi - Final thesis.pdf||Thesis||8.06 MB||Adobe PDF|
Items in Sydney eScholarship Repository are protected by copyright, with all rights reserved, unless otherwise indicated.