A team of researchers including Sarah R. Gilman and Ivan Iossifov of Columbia University and Cold Spring Harbor Laboratory, respectively have just published a paper in the influential journal, Neuron providing evidence that autism-associated rare Copy Number Variant (CNV) Mutations (a gene mutations in which there are varying copies of a segment of the gene) form a functional network of genes that are related to synapse development, axon targeting, and neuron motility.
The paper titled ‘Rare De Novo Variants Associated with Autism Implicate a Large Functional Network of Genes Involved in Formation and Function of Synapses’ describe their work using a sophisticated technique called network modeling, to identify the network and demonstrated its association with genes previously implicated in autism and intellectual disability phenotypes. The other authors of this paper include Dan Levy, Michael Ronemus, Michael Wigler, and Dennis Vitkup (the lead investigator) of Columbia University.This paper is one in the series of papers published in the journal yesterday describing details of the genetic basis of Autism.
Why is this Study Important?
As the paper explains, “Although autism has a very strong genetic component, with an estimated heritability as high as 90% based on studies of monozygotic twins, genome studies have implicated only a few genes. The underlying genetic determinants for this disease still remain largely unknown”
This paper and the other two have provided ground breaking evidence (as reported by the Time) that “Random changes in genes, rather than changes handed down from parents, may be responsible for some cases of autism. What they found was that children with autism were about four times more likely than their unaffected siblings to have copy number variants (CNVs), mutations in which a part of the genome is either duplicated or deleted. The CNVs in children with autism were also larger and contained a higher density of genes than the CNVs in unaffected siblings.
Specifically, Gilman and Iossifov used Network Modeling, a statistical and mathematical method to create a network of the numerous random mutations and their association with functional pathways that effect neuronal development. They also demonstrated that girls have more CNVs than boys and these CNVs involve more genes. This probably illustrates that they have a higher threshold for developing autism than boys and thus explains why autism is more common in boys than girls.
How does this study Benefit those with autism or lead to a treatment?
These three studies throw light on the causation of the disease and providing a better understanding of the basis of Autism. As Dr. matthew State, Professor of Child Psychiatry and Genetics at Yale University stated to Time, “These genetic studies open the door to understanding the biology and pathophysiology of the disorder and It lays an important foundation for the next step, which is to identify better treatments for folks with autism.”
Autism spectrum disorders are characterized by impaired social interactions, abnormal verbal communication, restricted interests, and repetitive behaviors. Due in part to better detection strategies, the combined prevalence of ASD has been steadily increasing for several decades and is nowapproaching a staggering 1% in the human population.