Burden of rare genetic variants in movement disorders and other related neurological conditions
Movement disorders are common neurological disorders. For example, tics can be found in 4%-19% in children. However, majority of the individuals with movement disorders do not have a genetic cause determined. Our aim is to conduct a genetic study of the children who do not currently have a genetic cause of their movement disorders identified. Genome sequencing technology has allowed detection of causal genetic factors in a subset of these disorders, but the causes in most of the cases are still unknown. This can be due to the neglection of repetitive DNA regions, which constitute most of our genetic information. There are over 50 genetic disorders currently linked to abnormality in repetitive sequence. They are mostly caused by increased length of the repeats (repeat expansions). We will adopt a genetic approach that has been successfully applied on other disorders, such as autism. We will 1) identify and validate tandem repeat expansions in movement disorders, and 2) annotate the identified tandem repeats for possible functional roles in movement disorders. By reviewing these cases and compare them with those in the UK Biobank in the next 3 years, we hope to be able to identify genetic changes in order to find genes that are relevant to movement disorders or their related conditions, and ultimately improve the medical management and treatment for the children.