The use of next generation sequencing technologies to dissect the aetiologies of Parkinson's disease and dystonia

• Main Author: Sheerin, U.
• Published: University College London (University of London) 2014
• Subjects: 616.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.631867

Whole exome sequencing (WES) – the targeted sequencing of the subset of the human genome that is protein coding – is a powerful and cost-effective new tool for dissecting the genetic basis of diseases and traits, some of which have proved to be intractable to conventional gene-discovery strategies. My PhD thesis focuses on the use of whole exome sequencing to dissect the genetic aetiologies of families with Mendelian forms of Parkinson’s disease and Dystonia. First I present a project where next generation sequencing played an important role in the identification of a novel Parkinson’s disease gene (VPS35). I then describe the use of WES in i) an autosomal dominant PD kindred, where a novel DCTN1 mutation was identified; and show a number of examples of successes and failures of WES in ii) autosomal recessive Parkinson’s disease and iii) autosomal recessive generalised dystonia.