Study of copy number variants in autism spectrum disorders and their comorbidities

Autism Spectrum Disorders (ASDs) are a group of multifactorial, heterogeneous neurodevelopmental disorders characterized by deficits in communication and social interaction, and repetitive behaviors. The prevalence is ~1% worldwide with a 4:1 male to female ratio. Several co-morbidities have been associated with Autism Spectrum Disorders including intellectual disability, craniofacial malformations, head circumference defects (micro/macrocephaly), gastrointestinal problems, and heart malformations.
CNVs (e.g. deletion, duplication, insertion, inversion) represent the most frequent types of genetic lesion in both rare and common human genetic disorders. To date, a total of 17 recurrent CNVs have been associated with ASD. The interpretation of these lesions is both acute and challenging. The primary focus in our laboratory is to understand how genetic variation can impact the development and homeostasis of the nervous system. To this goal, we have developed animal models and assays to study the impact of gene dosage defects on basic neurodevelopmental processes to:

• Discover genes and alleles that contribute to diseases
• Capture and validate genetic interactions (cis- and trans-modulators)
• Identify genes implicated in ASD-associated comorbidities 

The laboratory employs an innovative orthogonal approach to tackle the current challenges in the field by combining in vivo modeling in the developing zebrafish, mouse and genomic tools. Ultimately, our work will contribute to the stratification of this highly heterogeneous group of disorders and will, in turn, inform diagnosis and patient care.