Genetic interactions are responsible for neurodevelopmental disorders, a recent study has found.

Genes located in a large chromosomal aberration, associated with autism, interact with each other to modulate the variable symptoms of the disease. A team, led by Penn State researchers, tested the role of these genes individually. "As opposed to diseases that are caused by mutations in single genes, autism and other neurodevelopmental disorders have a complex etiology that can be the result of many interacting genes," said the lead author of the paper, Santhosh Girirajan.

Many neurodevelopmental disorders including autism, schizophrenia, and intellectual disability are associated with duplications of relatively large regions of chromosomes that contain many genes. The researchers focused on a large deletion on chromosome 16 that spans over 500,000 base pairs of As, Ts, Cs, and Gs that make up double-stranded DNA and was first discovered in individuals with autism.

The researchers turned to the fruit fly, Drosophila melanogaster, to try to identify how the deletion on chromosome 16 was causing these symptoms. "Although we only tested the 14 fly counterparts of the 25 human genes, our results suggest a model that can be applied to the overall mechanism of disease caused due to this deletion," said a postdoctoral researcher in the Girirajan lab and an author of the paper, Janani Iyer.

Using a technique called RNA interference in which a short piece of RNA can be designed to reduce the expression of a particular gene in either the entire fly or in a particular tissue, the researchers first tested each of the individual genes in the chromosome 16 deletion that have counterparts in the fly.

"Based on our results, we suggest a new model for the pathogenicity of the chromosome 16 deletion and other large regions of copy number variation in the genome," said Girirajan. He added, "We must consider the interactions among many genes to understand the variable symptoms associated with these large deletions, rather than looking for single causative genes. Understanding this will help us identify appropriate targets for possible treatment of these neurodevelopmental disorders." The full findings are published in the journal- Nature Communications.