Discovering Copy Number Variants Associated With Autism In Hispanic Families

Copy-number variants (CNVs) are segments of DNA in which copy-number differences have been found by comparison of two or more genomes. CNVs are also a source of human genetic variation and have spurred continued interest given their relationship with disease phenotypes. We now know that specific genomic architecture predisposes certain individuals to recurrent genomic arrangements that result in a wide array of disorders. For example, microdeletions of 17q21.31 and 16p12.1 have been linked to developmental delay. Furthermore, such recurrent genomic rearrangements may result in various neurodevelopmental disorders, including intellectual disability, autism, schizophrenia, epilepsy, as well as cardiac disease. Most CNV studies to date have been restricted to Caucasian populations; therefore, enrichment for CNVs among underrepresented groups such as Hispanic Americans has not been comprehensively documented. Here, we sought to identify and characterize genomic rearrangements among Hispanic American families afflicted with autism. Additional study objectives were to determine the frequency and localization of large CNVs among Hispanic Americans with autism compared to Caucasians with autism; and determine the mechanism of inheritance (i.e., inherited versus de novo) of potentially pathogenic rearrangements that are private to Hispanic American families. We used array comparative genomic hybridization on a sample set of 157 Hispanic Americans (74 cases, 83 controls) to identify potentially pathogenic CNVs. In total, we discovered 180 duplications and 56 deletions. We have successfully identified both genomic rearrangements that have been previously associated with autism in Caucasian populations as well as novel rearrangements that we believe to be private to Hispanic American families.