Evidence for differential alternative splicing in blood of young boys with autism spectrum disorders

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• 作者：Boryana S Stamova (1) (2) (5)
  Yingfang Tian (1) (2) (4)
  Christine W Nordahl (1) (3)
  Mark D Shen (1) (3)
  Sally Rogers (1) (3)
  David G Amaral (1) (3)
  Frank R Sharp (1) (2)
  
• 关键词：Autism ; ASD ; RNA ; Splicing ; Head size ; Gene expression
• 刊名：Molecular Autism
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：4
• 期：1
• 全文大小：1,410 KB
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• 作者单位：Boryana S Stamova (1) (2) (5)
  Yingfang Tian (1) (2) (4)
  Christine W Nordahl (1) (3)
  Mark D Shen (1) (3)
  Sally Rogers (1) (3)
  David G Amaral (1) (3)
  Frank R Sharp (1) (2)
  
  1. MIND Institute, University of California at Davis, Sacramento, CA, 95817, USA
  2. Department of Neurology, University of California at Davis, Sacramento, CA, 95817, USA
  5. MIND Institute Research Wet Labs, University of California at Davis, Room 2417, 2805 50th Street, Sacramento, CA, 95817, USA
  4. College of Life Sciences, Shaanxi Normal University, Xi’an, 710062, China
  3. Department of Psychiatry and Behavioral Sciences, University of California at Davis, Sacramento, CA, 95817, USA
  
• ISSN：2040-2392

文摘

Background Since RNA expression differences have been reported in autism spectrum disorder (ASD) for blood and brain, and differential alternative splicing (DAS) has been reported in ASD brains, we determined if there was DAS in blood mRNA of ASD subjects compared to typically developing (TD) controls, as well as in ASD subgroups related to cerebral volume. Methods RNA from blood was processed on whole genome exon arrays for 2-4–year-old ASD and TD boys. An ANCOVA with age and batch as covariates was used to predict DAS for ALL ASD (n=30), ASD with normal total cerebral volumes (NTCV), and ASD with large total cerebral volumes (LTCV) compared to TD controls (n=20). Results A total of 53 genes were predicted to have DAS for ALL ASD versus TD, 169 genes for ASD_NTCV versus TD, 1 gene for ASD_LTCV versus TD, and 27 genes for ASD_LTCV versus ASD_NTCV. These differences were significant at P <0.05 after false discovery rate corrections for multiple comparisons (FDR <5% false positives). A number of the genes predicted to have DAS in ASD are known to regulate DAS (SFPQ, SRPK1, SRSF11, SRSF2IP, FUS, LSM14A). In addition, a number of genes with predicted DAS are involved in pathways implicated in previous ASD studies, such as ROS monocyte/macrophage, Natural Killer Cell, mTOR, and NGF signaling. The only pathways significant after multiple comparison corrections (FDR <0.05) were the Nrf2-mediated reactive oxygen species (ROS) oxidative response (superoxide dismutase 2, catalase, peroxiredoxin 1, PIK3C3, DNAJC17, microsomal glutathione S-transferase 3) and superoxide radical degradation (SOD2, CAT). Conclusions These data support differences in alternative splicing of mRNA in blood of ASD subjects compared to TD controls that differ related to head size. The findings are preliminary, need to be replicated in independent cohorts, and predicted alternative splicing differences need to be confirmed using direct analytical methods.