Structure
Findings from genetic studies of autism spectrum disorder (ASD) reflect a central divergence as to whether the majority of genetic risk arises from common variation that is frequent but with low penetrance, or from rare variation with a high degree of penetrance and large effect. ASD is characterized by a high degree of both genetic and phenotypic heterogeneity. Despite long-standing evidence that ASD is a highly heritable, polygenic disorder, there still remains some uncertainty about the full allelic spectrum that underlies ASD.
With the advent of next-generation sequencing technologies, researchers have focused on the contribution of de novo variation through whole exome sequencing (WES) studies and genome-wide genotyping arrays to identify rare single nucleotide variants (SNVs), insertion-deletions (indels), and copy number variants (CNVs) associated with ASD. The identification of such variation in ASD-diagnosed individuals has resulted in the discovery of dozens of...
This is a preview of subscription content, log in via an institution to check access.
References and Readings
Bucan, M., Abrahams, B. S., Wang, K., Glessner, J. T., Herman, E. I., Sonnenblick, L. I., et al. (2009). Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes. PLoS Genetics, 5(6), e1000536.
Cotney, J., Muhle, R. A., Sanders, S. J., Liu, L., Willsey, A. J., Niu, W., et al. (2015). The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nature Communications, 6, 6404.
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y., Mele, A., Fraser, C. E., et al. (2011). FMRP stalls ribosomal translocation on mRNAs linked to synaptic function and autism. Cell, 146(2), 247–261.
De Rubeis, S., He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Cicek, A. E., et al. (2014). Synaptic, transcriptional and chromatin genes disrupted in autism. Nature, 515(7526), 209–215.
Dong, S., Walker, M. F., Carriero, N. J., DiCola, M., Willsey, A. J., Ye, A. Y., et al. (2014). De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder. Cell Reports, 9(1), 16–23.
Gaugler, T., Klei, L., Sanders, S. J., Bodea, C. A., Goldberg, A. P., Lee, A. B., et al. (2014). Most genetic risk for autism resides with common variation. Nature Genetics, 46(8), 881–885.
Geschwind, D. H., & State, M. W. (2015). Gene hunting in autism spectrum disorder: on the path to precision medicine. Lancet Neurology, 14(11), 1109–1120.
Iossifov, I., O’Roak, B. J., Sanders, S. J., Ronemus, M., Krumm, N., Levy, D., et al. (2014). The contribution of de novo coding mutations to autism spectrum disorder. Nature, 515(7526), 216–221.
Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., et al. (2012). De novo gene disruptions in children on the autistic spectrum. Neuron, 74(2), 285–299.
Klei, L., Sanders, S. J., Murtha, M. T., Hus, V., Lowe, J. K., Willsey, A. J., et al. (2012). Common genetic variants, acting additively, are a major source of risk for autism. Mol Autism, 3(1), 9.
Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., Brune, C., Badner, J. A., et al. (2008). Recurrent 16p11.2 microdeletions in autism. Human Molecular Genetics, 17(4), 628–638.
Marshall, C. R., Noor, A., Vincent, J. B., Lionel, A. C., Feuk, L., Skaug, J., et al. (2008). Structural variation of chromosomes in autism spectrum disorder. American Journal of Human Genetics, 82(2), 477–488.
Mefford, H. C., Sharp, A. J., Baker, C., Itsara, A., Jiang, Z., Buysse, K., et al. (2008). Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. The New England Journal of Medicine, 359(16), 1685–1699.
Moreno-De-Luca, D., Sanders, S. J., Willsey, A. J., Mulle, J. G., Lowe, J. K., Geschwind, D. H., et al. (2013). Using large clinical data sets to infer pathogenicity for rare copy number variants in autism cohorts. Molecular Psychiatry, 18(10), 1090–1095.
Neale, B. M., Kou, Y., Liu, L., Ma’ayan, A., Samocha, K. E., Sabo, A., et al. (2012). Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature, 485(7397), 242–245.
O’Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., et al. (2011). Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nature Genetics, 43(6), 585–589.
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., et al. (2012). Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature, 485(7397), 246–250.
Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., et al. (2014). Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. American Journal of Human Genetics, 94(5), 677–694.
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., et al. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature, 466(7304), 368–372.
Saha, S., Barnett, A. G., Foldi, C., Burne, T. H., Eyles, D. W., Buka, S. L., et al. (2009). Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood. PLoS Medicine, 6(3), e40.
Sanders, S. J., Ercan-Sencicek, A. G., Hus, V., Luo, R., Murtha, M. T., Moreno-De-Luca, D., et al. (2011). Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron, 70(5), 863–885.
Sanders, S. J., He, X., Willsey, A. J., Ercan-Sencicek, A. G., Samocha, K. E., Cicek, A. E., et al. (2015). Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Neuron, 87(6), 1215–1233.
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., et al. (2012). De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature, 485(7397), 237–241.
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., et al. (2007). Strong association of de novo copy number mutations with autism. Science, 316(5823), 445–449.
Sugathan, A., Biagioli, M., Golzio, C., Erdin, S., Blumenthal, I., Manavalan, P., et al. (2014). CHD8 regulates neurodevelopmental pathways associated with autism spectrum disorder in neural progenitors. Proceedings of the National Academy of Sciences of the United States of America, 111(42), E4468–E4477.
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., et al. (2008). Association between microdeletion and microduplication at 16p11.2 and autism. The New England Journal of Medicine, 358(7), 667–675.
Willsey, A. J., Sanders, S. J., Li, M., Dong, S., Tebbenkamp, A. T., Muhle, R. A., et al. (2013). Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell, 155(5), 997–1007.
Zoghbi, H. Y., & Bear, M. F. (2012). Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harbor Perspectives in Biology, 4(3), a009886.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media LLC
About this entry
Cite this entry
Oliphant, M., Fernandez, T. (2017). Gene Regulatory Networks in Autism. In: Volkmar, F. (eds) Encyclopedia of Autism Spectrum Disorders. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6435-8_102153-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-6435-8_102153-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-6435-8
Online ISBN: 978-1-4614-6435-8
eBook Packages: Springer Reference Behavioral Science and PsychologyReference Module Humanities and Social SciencesReference Module Business, Economics and Social Sciences