Rare De Novo Variants Associated with Autism Implicate a Large Functional Network of Genes Involved in Formation and Function of Synapses

Gilman, S. R, Iossifov, I., Levy, D., Ronemus, M., Wigler, M. H., Vitkup, D. (2011) Rare De Novo Variants Associated with Autism Implicate a Large Functional Network of Genes Involved in Formation and Function of Synapses. Neuron, 70 (5). pp. 898-907. ISSN 0896-6273

URL: http://www.ncbi.nlm.nih.gov/pubmed/21658583
DOI: 10.1016/j.neuron.2011.05.021

Abstract

Summary Identification of complex molecular networks underlying common human phenotypes is a major challenge of modern genetics. In this study, we develop a method for network-based analysis of genetic associations (NETBAG). We use NETBAG to identify a large biological network of genes affected by rare de novo CNVs in autism. The genes forming the network are primarily related to synapse development, axon targeting, and neuron motility. The identified network is strongly related to genes previously implicated in autism and intellectual disability phenotypes. Our results are also consistent with the hypothesis that significantly stronger functional perturbations are required to trigger the autistic phenotype in females compared to males. Overall, the presented analysis of de novo variants supports the hypothesis that perturbed synaptogenesis is at the heart of autism. More generally, our study provides proof of the principle that networks underlying complex human phenotypes can be identified by a network-based functional analysis of rare genetic variants.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > analysis and processing
bioinformatics > genomics and proteomics > analysis and processing > NETBAG
diseases & disorders > mental disorders > personality disorders > autism
CSHL Authors:
Communities: CSHL labs > Wigler lab
CSHL labs > Iossifov lab
CSHL labs > Levy lab
CSHL Cancer Center Shared Resources > Instrumentation Service
Depositing User: CSHL Librarian
Date Deposited: 09 Nov 2011 17:31
Last Modified: 07 Apr 2015 16:35
PMCID: PMC3607702
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15635

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