Resumen de Contribution of unexplored genomic variants to neurodevelopmental disorders
Neurodevelopmental disorders are a group of conditions with impairments of the personal, social, academic or occupational behaviour. Autism spectrum disorder is a neurodevelopmental disorder with a high genetic component with a large fraction still unknown. In this dissertation we analyse two unexplored genomic variants: Chromosomal mosaicism and Ancestral polymorphic inversions. Chromosomal mosaic events are responsible for a small but significant proportion of patients with ASD (0.45%), with the additional detection of two loss of chromosome Y events. In addition, we developed a bioinformatic tool that improves previous methods to detect loss of chromosome Y: MADloy. In the study of ancestral polymorphic inversions, inv8p23.1 and inv17q21.31 inversions were associated with autism risk. Improvements on the method to genotype ancestral polymorphic inversions allowed the prediction of a novel inversion in 22q11.21 region which has been validated by fiber-FISH.
