HIGH RESOLUTION ARRAY-CGH AND GENE EXPRESSION ANALYSES IN AUTISM SPECTRUM DISORDERS

Autism spectrum disorders (ASDs) are characterized by impairment in social interactions, deficit in verbal and nonverbal communication, and repetitive and stereotyped patterns of behaviours, interests and activities. ASDs are considered one of the most prevalent heritable complex diseases. Several evidences suggest that ASDs have strong genetic bases but very few genes implicated in this disease have been identified. The aim of this project is to detect genomic alterations in patients with autism spectrum disorders and to define their pathological role. Array-based comparative genome hybridization (array-CGH) is a powerful technique to unveil genomic rearrangements, such as deletions and duplications. The efficacy of this technique has already been shown by other studies on autistic subjects which revealed cryptic imbalances in about 10% of sporadic cases and 2%-3% of familial cases. The purpose of this project is to investigate 280 autistic subjects by high-resolution array-CGH in order to highlight genomic imbalances, also known as copy number variations (CNVs), which may underlie this disease. All CNVs potentially causative of ASDs will be investigated by in silico and statistical analyses. Additionally, gene expression analysis on RNA from these individuals will be carried out so as to figure out the pathological role of such CNVs. Although the molecular bases of ASDs still remain largely unknown, from this study we expect to identify new insights into the biological processes leading to autism.