PhD defence R. (Ruizhi) Deng

Brief summary:

Neurodevelopmental disorders (NDDs) affect more than 3% of the population worldwide, impacting largely on the affected individuals, families, society and the health care systems. Multiple etiologies underlie the development of these disorders, with a prominent place for genetics with more than 1,500 genes currently implicated in NDDs when mutant. Despite an enormous technological progress in the field of human genetics, allowing to sequence all coding genes (e.g., the exome) and even the complete genome of individuals in a quest to identify the underlying genetic cause, at present still more than half of the affected individuals remain without a genetic diagnosis even when there is a high clinical suspicion of a genetic disorder. This missing heritability is a considerable problem in the field, as without a genetic diagnosis no proper counseling of affected individuals and their families is possible, informed reproductive choices are limited for parents, and tailored clinical care and personalized medicine options are reduced. Various factors can contribute to this missing heritability, including technical and computational shortcoming that do not allow to identify the genetic cause, and the remaining gap of knowledge on both coding genes and the role of the non-coding genome in causing NDDs. In this thesis, I address some of these aspects to help reducing missing heritability in NDDs and other rare disorders.