Autism researchers at Columbia University Medical Center have identified hundreds of genes that, when mutated, likely increase the risk of developing autism spectrum disorder (ASD). The variability among people with ASD is thought to stem from the diversity of underlying genetic changes, including the specific genes mutated and the severity of the mutation.
Senior author Dennis Vitkup, PhD said, "If we can understand how different mutations lead to different features of ASD, we may be able to use patients' genetic profiles to develop accurate diagnostic and prognostic tools and perhaps personalize treatment."
To investigate the links between genetic mutations and autism traits, researchers analyzed genetic and clinical data on hundreds of patients with ASD. They found that IQ and gender differences in autism are influenced by severity of mutations. People with more damaging genetic mutations usually lead to worse disease outcomes. Gender differences in autism cases could also be traced to the type of genes mutated in the individual.
Patients with low-verbal or nonverbal IQs usually had mutations in genes that are more active in the brain, and high-IQ individuals were less likely to have mutations that completely shut down genes, while mutations that only partially damage normal gene function in the brain appear to be predominantly associated with high-functioning autism cases. Researchers also found that the genes mutated in females generally had greater activity throughout the brain than those mutated in males.
The research team identified the type of affected brain cells by looking at the normal activity of autism-related genes in dozens of similar cell types in mouse brains. Their analysis showed that many different types of neurons throughout the brain are affected by mutations in autism genes.
Dr. Vitkup said, "The idea that eventually all autism mutations would converge onto a single type of neuron or single brain area isn't what we see in the data. Instead, an autism mutation usually affects multiple brain areas simultaneously."
The cortical and striatal neurons that form a circuit that controls repetitive motions and behaviors, such as rocking, an insistence on sameness, and restricted interests, which are common in people with ASD, seem to be affected more.
The study titled 'Genotype to phenotype relationships in autism spectrum disorders' is published in the journal 'Nature Neuroscience'.