Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism
Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaq...
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| Veröffentlicht in: | PLoS biology 2016-09, Vol.14 (9), p.e1002558-e1002558 |
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| creator | Liu, Xiling Han, Dingding Somel, Mehmet Jiang, Xi Hu, Haiyang Guijarro, Patricia Zhang, Ning Mitchell, Amanda Halene, Tobias Ely, John J Sherwood, Chet C Hof, Patrick R Qiu, Zilong Pääbo, Svante Akbarian, Schahram Khaitovich, Philipp |
| description | Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans. |
| doi_str_mv | 10.1371/journal.pbio.1002558 |
| format | Article |
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Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.1002558</identifier><identifier>PMID: 27685936</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Autism ; Biology ; Biology and Life Sciences ; Brain research ; Funding ; Gene expression ; Genetic aspects ; Health aspects ; Laboratories ; Macaca ; Medicine ; Medicine and Health Sciences ; Mutation ; Neurosciences ; Pan troglodytes ; Physical Sciences ; Research and Analysis Methods ; Science ; Social Sciences ; Socialization</subject><ispartof>PLoS biology, 2016-09, Vol.14 (9), p.e1002558-e1002558</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Liu X, Han D, Somel M, Jiang X, Hu H, Guijarro P, et al. (2016) Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism. PLoS Biol 14(9): e1002558. doi:10.1371/journal.pbio.1002558</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Liu X, Han D, Somel M, Jiang X, Hu H, Guijarro P, et al. (2016) Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism. 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| subjects | Autism Biology Biology and Life Sciences Brain research Funding Gene expression Genetic aspects Health aspects Laboratories Macaca Medicine Medicine and Health Sciences Mutation Neurosciences Pan troglodytes Physical Sciences Research and Analysis Methods Science Social Sciences Socialization |
| title | Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism |
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