Genome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder.
A genome-wide differential expression of long noncoding RNAs (lncRNAs) was identified in blood specimens of autism spectrum disorder (ASD). A total of 3929 lncRNAs were found to be differentially expressed in ASD peripheral leukocytes, including 2407 that were upregulated and 1522 that were downregulated. Simultaneously, 2591 messenger RNAs (mRNAs), including 1789 upregulated and 821 downregulated, were also identified in ASD leukocytes. Functional pathway analysis of these lncRNAs revealed neurological pathways of the synaptic vesicle cycling, long-term depression and long-term potentiation to be primarily involved. Thirteen synaptic lncRNAs, including nine upregulated and four downregulated, and 19 synaptic mRNAs, including 12 upregulated and seven downregulated, were identified as being differentially expressed in ASD. Our identification of differential expression of synaptic lncRNAs and mRNAs suggested that synaptic vesicle transportation and cycling are important for the delivery of synaptosomal protein(s) between presynaptic and postsynaptic membranes in ASD. Finding of 19 lncRNAs, which are the antisense, bi-directional and intergenic, of HOX genes may lead us to investigate the role of HOX genes involved in the development of ASD. Discovery of the lncRNAs of SHANK2-AS and BDNF-AS, the natural antisense of genes SHANK2 and BDNF, respectively, indicates that in addition to gene mutations, deregulation of lncRNAs on ASD-causing gene loci presents a new approach for exploring possible epigenetic mechanisms underlying ASD. Our study also opened a new avenue for exploring the use of lncRNA(s) as biomarker(s) for the early detection of ASD.
Department of Child Health Care, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China.
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Wang
Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China.|Peking University Center of Medical Genetics, Beijing, China.
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Zhao
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
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Ju
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
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Flory
Student volunteer, Hunter College High School, New York, NY, USA.
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Zhong
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Jiang
Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China.|Peking University Center of Medical Genetics, Beijing, China.
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Wang
Department of Child Health Care, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China.
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Dong
Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China.|Peking University Center of Medical Genetics, Beijing, China.
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Tao
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Chen
Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China.|Peking University Center of Medical Genetics, Beijing, China.
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Shen
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Zhong
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
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Yu
Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
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Brown
Department of Child Health Care, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.|Chinese Alliance of Translational Medicine for Maternal and Children's Health, Beijing, China.|Peking University Center of Medical Genetics, Beijing, China.|Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.|Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China.|March of Dimes Global Network for Maternal and Infant Health, White Plains, NY, USA.
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Zhong
D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D062085:RNA, Long Noncoding / Q000235:genetics*
D062085:RNA, Long Noncoding