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 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.
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.|Big Data Decision Institute, Jinan University, Guangzhou, China.|Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Sciences, Ministry of Justice, Shanghai, China.
Xiling
X
Liu
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.
Dingding
D
Han
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.|Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.
Mehmet
M
Somel
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.
Xi
X
Jiang
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.
Haiyang
H
Hu
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.
Patricia
P
Guijarro
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.
Ning
http://orcid.org/0000-0002-8782-7806
N
Zhang
Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Amanda
A
Mitchell
Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Tobias
http://orcid.org/0000-0003-1944-4683
T
Halene
MAEBIOS-TM, Alamogordo, New Mexico, United States of America.
John J
JJ
Ely
Department of Anthropology, The George Washington University, Washington, District of Columbia, United States of America.
Chet C
CC
Sherwood
Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Patrick R
PR
Hof
Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China.
Zilong
Z
Qiu
Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Svante
S
Pääbo
Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Schahram
S
Akbarian
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai, China.|Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.|Skolkovo Institute for Science and Technology, Skolkovo, Russia.
Philipp
P
Khaitovich
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