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Identify Down syndrome transcriptome associations using integrative analysis of microarray database and

Min Chen1,2,3,4,5, Jiayan Wang1,2,3,4, Yingjun Luo6

  • 1Department of Fetal Medicine and Prenatal Diagnosis, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.

Human Genomics
|January 21, 2018
PubMed
Summary
This summary is machine-generated.

Down syndrome-associated gene DSCR9, a long non-coding RNA (lncRNA), is linked to neurological functions. Our bioinformatics analysis reveals DSCR9

Keywords:
Correlation-interaction-networkDSCR9Down syndromeNeurological diseasesProtein–protein interactionlncRNA

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Area of Science:

  • Genomics
  • Bioinformatics
  • Neuroscience

Background:

  • Long non-coding RNAs (lncRNAs) play crucial roles in biological processes.
  • Dysregulation of lncRNAs is associated with human diseases, including neurological disorders.
  • DSCR9, a lncRNA from the Down syndrome critical region (DSCR) on chromosome 21, is implicated in Down syndrome.

Purpose of the Study:

  • To investigate the functions of the Down syndrome-associated gene DSCR9 and its lncRNAs using a multi-step bioinformatics approach.
  • To develop and apply a novel pipeline, Correlation-Interaction-Network (COIN), for analyzing lncRNA functions.
  • To explore the co-expression gene network and biological network associated with DSCR9.

Main Methods:

  • Utilized a large dataset of over 1700 Affymetrix human microarray sets (nearly 60,000 samples) from the EBI database.
  • Employed a Correlation-Interaction-Network (COIN) pipeline integrating co-expression gene network analysis and protein-protein interaction (PPI) network information.
  • Performed enrichment analysis (KEGG, GO) to identify significantly correlated pathways and validated co-expressed genes using qPCR in cell lines with DSCR9 overexpression.

Main Results:

  • DSCR9 co-expression genes are significantly associated with neuro-active ligand-receptor interactions, calcium signaling pathways, and neuronal system functions.
  • Key genes identified include GLP1R, HTR4, P2RX2, UCN3, UTS2R, CACNA1F, CACNG4, SLC8A3, KCNJ5, and SYN1.
  • qPCR validation confirmed the expression of 10 DSCR9 co-expressed genes with over 70% accuracy in cell lines overexpressing DSCR9.

Conclusions:

  • DSCR9 is highly correlated with genes critical for nervous system development and function.
  • DSCR9 potentially regulates neurological proteins relevant to Down syndrome and other neurological disorders.
  • The developed bioinformatics pipeline is adaptable for analyzing other lncRNAs and their functions.