Genome-wide Investigation of Rare Genetic Variation in Epilepsy and Autism Spectrum Disorder
Year: 2020
Type: dissertation
Study design: Observational Study
Abstract: Epilepsy and autism spectrum disorder (ASD) are a clinically heterogeneous group of neurological disorders. Despite their known genetic basis, many cases of epilepsy and ASD remain unresolved without a molecular diagnosis. In this thesis, I describe the use of whole-genome sequencing (WGS) to conduct a genome-wide investigation of rare genetic variation in two cohorts. In a cohort of unexplained epilepsies, I identified clinically relevant rare variants in 9/28 (32.1%) participants, for whom prior genetic tests were inconclusive. In a cohort of 20 participants with a duplication of the 7q11.23 region (Dup7), I found that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7-ASD phenotype. Overall, my findings demonstrate that the use of WGS enables molecular diagnosis, points to the role of multiple contributing variants in the genetic background, and yields insights into epilepsy-ASD genetics.
Source: TSpace (University of Toronto)
Author: Farah Qaiser
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3136691387