The genetics of spinocerebellar ataxia and dystoniaNibbeling, E., 2017, [Groningen]: Rijksuniversiteit Groningen. 195 p.
Research output: Thesis › Thesis fully internal (DIV)
Spinocerebellar ataxia and dystonia are movement disorders that affect the movement patterns and coordination of the patients. Although these are separate disorders, they show a large overlap in molecular etiology. Both disorders are genetically heterogeneous, meaning that they can be caused by mutations in a variety of genes. However, for many patients the genetic cause is not found in regular DNA diagnostics, because more genes are involved in the etiology of these disorders than are currently known. In this thesis I describe the process of novel disease gene identification for spinocerebellar ataxia and dystonia. To achieve this, we mainly used so-called ‘next generation sequencing’ techniques that allow for simultaneous testing of multiple genes. These methods render a large amount of data and finding the disease-causing variant is quite a challenge. Therefore, we have also used bioinformatic gene network analysis and functional tests in cell models to strengthen our data. In the end, we have identified seven novel genes that can cause spinocerebellar ataxia and a mutation in a gene that can cause writer’s cramp, directly improving genetic diagnostics for the patients. Additionally, the function of these genes expose that transcription regulation and synaptic transmission are important disease mechanisms underlying movement disorders such as ataxia and dystonia.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2017|
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