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NJIT Mathematical Biology Seminar

Tuesday, Apri 12, 2011, 2:30pm
Cullimore Hall 611
New Jersey Institute of Technology

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Rare de novo variants associated with autism perturb a large network of genes involved in formation and function of synapses

Ivan Iossifov

Cold Spring Harbor Lab

Recent evidence suggests that rare variants, including copy number variations (CNVs), play a significant role in the heritability of autism. In this study we develop a method for NETwork-Based Analysis of Genetic associations (NETBAG). We use the method to identify a large biological network significantly perturbed by rare de novo CNVs in autism. The identified network is primarily related to synapse development, axon targeting, and neuron motility. Our results are consistent with the hypothesis that significantly stronger functional perturbations are required to trigger the autistic phenotype in females compared to males. The perturbed network is strongly functionally related to genes previously implicated in autism and genes associated with intellectual disability phenotypes. More generally, our study provides a proof of the principle that networks underlying complex phenotypes can be identified by a functional analysis of rare genetic variants observed in a large collection of affected individuals.