Neurodevelopmental Disorders (NDDs) are a group of prevalent and highly heterogeneous disorders characterized by perturbed brain development resulting in alterations in motor function, learning, language, and/or nonverbal communication. Based on large-scale exome and whole-genome sequencing studies conducted in the last decade, it is estimated that more than 1,000 genes conferring risk for NDDs have yet to be described. Overall, these complex set of diseases are characterized by considerable heterogeneity in clinical manifestations and genetic background. This highlights the critical importance of advancing new methods to stratify and characterize different etiologies and clinical profiles within subgroups, paving the way towards the development of treatments tailored to the specific pathophysiology of each group.
Recently, pathogenic structural variants (SVs), such as deletions, duplications or inversions, have been described as rare but highly penetrant genetic factors involved in the ethiology of different types of NDDs, such as autism, intellectual disability or schizophrenia. This type of variation can affect genomic areas of very different sizes, thus involving a wide range of dose-sensitive genes.
Consequently, meta-analyses of genomic data from large-scale patient cohorts play a key role in identifying SVs significantly associated with specific subgroups of neurodevelopmental disorders. In this project, we propose to conduct a large-scale computational analysis of genomic data to identify critical regions and genes within the SVs that are recurrently altered in subsets of patients with NDDs. Furthermore, this study aims to analyze the impact of these variants on brain morphology and to associate SVs with abnormalities that have already been reported in patients with neurodevelopmental conditions, such as cortical thickness, degree of gyrification or surface area. The results of the proposed large-scale analysis are likely to provide unprecedented insight into the relationship between genomic variants and the pathophysiology of various NDDs