Copy Number Variation in Verbal and Non-verbal patients with Autism Spectrum Disorders

Abstract

Twin and family studies have shown that autism spectrum disorders (ASD) are highly heritable (~ 92%), but its etiology is still unknown. This fact is due to ASD being a complex disorder , with heterogeneous phenotype and several genes involved in its etiology. Recently, both heritable and de novo copy number variations (CNVs) and point mutations (SNVs) were associated with ASD, suggesting new loci and candidate genes including those involved in neurodevelopment and language (SHANK3, CNTNAP2, CDH9 and CDH10). These studies, however, still have little replicability. An alternative to this lack of findings is to study structural changes of the genome in rare and common endophenotypes of ASD, ie, sub-components of measurable and inherited phenotype. Thus genetic studies associated with phenotypic traits, such as language, seems more promising for understanding the etiologic basis of ASD when compared with studies where complex phenotype may hinder the understanding of the genetic bases involved in ASD. This work will seek to determine whether there are rare and/or de novo CNVs and SNVs of ASD trios, in different subphenotypes related to language (verbal and nonverbal patients). The study intends to examine a possible association of these variations affecting genes and biological pathways involved in ASD, and will be conducted by exome sequencing technique on Illumina platform.