Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/103972
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Type: Theses
Title: The genetic determinants of cerebral palsy
Author: McMichael, Gai Lisette
Issue Date: 2016
School/Discipline: School of Medicine
Abstract: The main goal of genetic evaluation of individuals living with cerebral palsy is to understand the underlying origin of the disorder, so that those affected, their families and the wider community can benefit from further research leading to prevention, better management and ultimately, treatment. The advent of next generation sequencing technologies (NGS), in particular massively parallel sequencing, is a promising way forward in identifying the causes of, or contribution of genetic variation to, cerebral palsy. These technologies have been successful in increasing understanding of the causes of neurodevelopmental disorders whose phenotypes overlap with cerebral palsy (e.g. intellectual disability, autism and epilepsy), and provide an excellent way forward for cerebral palsy genetic research. However, they also bring with them new challenges, including determining which variants/genes are potentially pathogenic for cerebral palsy. We took an unbiased whole-exome sequencing approach to identify potential pathogenic variants for cerebral palsy in two groups of individuals with cerebral palsy: sporadic cases (no previous family history of cerebral palsy) and families with more than one individual with a confirmed diagnosis of cerebral palsy. Until our work, WES had only been performed in a small number of familial cases. Our overall findings suggest that cerebral palsy is genetically heterogeneous, involving mutations, mainly de novo, in previously known neurodevelopmental genes and novel candidate cerebral palsy genes. The de novo origin of these mutations may explain the typically sporadic nature of cerebral palsy, with most affected individuals having no apparent family history. De novo mutations are also associated with a sizable proportion of sporadic cases of ID and ASD and represent an important cause for both disorders.
Advisor: Gecz, Jozef
Haan, Eric Albert
Dissertation Note: Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2016.
Keywords: cerebral palsy
genetics
whole exome sequencing
Research by Publication
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals
DOI: 10.4225/55/58d205e315cc9
Appears in Collections:Research Theses

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