Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism

被引：60

作者：

Liu, Xiling ^{[1
,2
,3
]}

Han, Dingding ^{[1
]}

Somel, Mehmet ^{[1
,4
]}

Jiang, Xi ^{[1
]}

Hui, Haiyang ^{[1
]}

Guijarro, Patricia ^{[1
]}

Zhang, Ning ^{[1
]}

Mitchell, Amanda ^{[5
,6
]}

Halene, Tobias ^{[5
,6
]}

Ely, John J. ^{[7
]}

Sherwood, Chet C. ^{[8
]}

Hof, Patrick R. ^{[6
,9
]}

Qiu, Zilong ^{[10
]}

Paeaebo, Svante ^{[11
]}

Akbarian, Schahram ^{[5
,6
]}

Khaitovich, Philipp ^{[1
,11
,12
]}

机构：

[1] CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol, Shanghai, Peoples R China

[2] Jinan Univ, Big Data Decis Inst, Guangzhou, Guangdong, Peoples R China

[3] Minist Justice, Inst Forens Sci, Shanghai Key Lab Forens Med, Shanghai, Peoples R China

[4] Middle East Tech Univ, Dept Biol Sci, Ankara, Turkey

[5] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[7] MAEBIOS TM, Alamogordo, NM USA

[8] George Washington Univ, Dept Anthropol, Washington, DC USA

[9] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA

[10] Chinese Acad Sci, Inst Neurosci, Shanghai, Peoples R China

[11] Max Planck Inst Evolutionary Anthropol, Leipzig, Germany

[12] Skolkovo Inst Sci & Technol, Skolkovo, Russia

来源：

PLOS BIOLOGY | 2016年 / 14卷 / 09期

基金：

俄罗斯科学基金会; 中国国家自然科学基金; 中国博士后科学基金;

关键词：

HIGH-FUNCTIONING AUTISM; TRANSCRIPTION FACTOR; SPECTRUM DISORDERS; PREFRONTAL CORTEX; RETT-SYNDROME; BRAIN; GROWTH; GENE; CHILDREN; LIFE;

D O I：

10.1371/journal.pbio.1002558

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：23

共 70 条

[31]

2-Z

[32] Cortical activation and synchronization during sentence comprehension in high-functioning autism: evidence of underconnectivity [J].

Just, MA ;

Cherkassky, VL ;

Keller, TA ;

Minshew, NJ .

BRAIN, 2004, 127 :1811-1821

[33]

Kanner L, 1943, NERV CHILD, V2, P217

[34] MATCH™:: a tool for searching transcription factor binding sites in DNA sequences [J].

Kel, AE ;

Gössling, E ;

Reuter, I ;

Cheremushkin, E ;

Kel-Margoulis, OV ;

Wingender, E .

NUCLEIC ACIDS RESEARCH, 2003, 31 (13) :3576-3579

[35] A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK? [J].

Knapska, E ;

Kaczmarek, L .

PROGRESS IN NEUROBIOLOGY, 2004, 74 (04) :183-211

[36] Autism [J].

Lai, Meng-Chuan ;

Lombardo, Michael V. ;

Baron-Cohen, Simon .

LANCET, 2014, 383 (9920) :896-910

[37] Ultrafast and memory-efficient alignment of short DNA sequences to the human genome [J].

Langmead, Ben ;

Trapnell, Cole ;

Pop, Mihai ;

Salzberg, Steven L. .

GENOME BIOLOGY, 2009, 10 (03)

[38] Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory [J].

Li, Lin ;

Yun, Sung Hwan ;

Keblesh, James ;

Trommer, Barbara L. ;

Xiong, Huangui ;

Radulovic, Jelena ;

Tourtellotte, Warren G. .

MOLECULAR AND CELLULAR NEUROSCIENCE, 2007, 35 (01) :76-88

[39] Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques [J].

Liu, Xiling ;

Somel, Mehmet ;

Tang, Lin ;

Yan, Zheng ;

Jiang, Xi ;

Guo, Song ;

Yuan, Yuan ;

He, Liu ;

Oleksiak, Anna ;

Zhang, Yan ;

Li, Na ;

Hu, Yuhui ;

Chen, Wei ;

Qiu, Zilong ;

Paeaebo, Svante ;

Khaitovich, Philipp .

GENOME RESEARCH, 2012, 22 (04) :611-622

[40] Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2 [J].

Liu, Zhen ;

Li, Xiao ;

Zhang, Jun-Tao ;

Cai, Yi-Jun ;

Cheng, Tian-Lin ;

Cheng, Cheng ;

Wang, Yan ;

Zhang, Chen-Chen ;

Nie, Yan-Hong ;

Chen, Zhi-Fang ;

Bian, Wen-Jie ;

Zhang, Ling ;

Xiao, Jianqiu ;

Lu, Bin ;

Zhang, Yue-Fang ;

Zhang, Xiao-Di ;

Sang, Xiao ;

Wu, Jia-Jia ;

Xu, Xiu ;

Xiong, Zhi-Qi ;

Zhang, Feng ;

Yu, Xiang ;

Gong, Neng ;

Zhou, Wen-Hao ;

Sun, Qiang ;

Qiu, Zilong .

NATURE, 2016, 530 (7588) :98-+

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