Gilman, S. R, Iossifov, I., Levy, D., Ronemus, M., Wigler, M. H., Vitkup, D. (June 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
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: | 8 June 2011 |
| Date Deposited: | 09 Nov 2011 17:31 |
| Last Modified: | 07 Apr 2015 16:35 |
| PMCID: | PMC3607702 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15635 |
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