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Dissertation/Thesis Abstract

Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders (ASD) by miRNA expression profiling of lymphoblastoid cell lines
by Sarachana, Tewarit, M.S., The George Washington University, 2009, 119; 1460204
Abstract (Summary)

Autism spectrum disorders (ASD) are neurodevelopmental disorders with a pattern of qualitative abnormalities in three behavioral areas: reciprocal social interactions, communication, and restricted interests and repetitive behaviors. Gene expression profiling of monozygotic twins discordant in diagnosis or severity of autism revealed differentially expressed, neurologically relevant genes, suggesting that epigenetic factors, such as DNA methylation or miRNA, may be involved in ASD. In this study, global miRNA expression profiling using lymphoblastoid cell lines derived from 5 autistic individuals and their monozygotic co-twins and/or their siblings were performed using high-throughput miRNA microarray analysis. The majority of the significantly differentially expressed miRNAs were found to target genes highly involved in neurological functions and disorders. The potential targets, moreover, were also linked to gastrointestinal diseases and estrogen receptor signaling, including androgen and estrogen metabolism. A number of the predicted potential target genes were also found to be significantly differentially expressed in cDNA microarray analyses. Novel network prediction analyses of the potential target genes whose transcript levels show an inverse relationship to that of the respective putative regulatory miRNAs reveal association with autism and other co-morbid disorders, i.e. muscular dystrophy and gastrointestinal diseases. Many interesting biological functions implicated in autism, such as memory and synaptic plasticity, were also highlighted. Findings from this study strongly suggest that dysregulation of miRNA expression is a contributing factor to the observed alterations in gene expression and, in turn, may lead to the pathophysiological conditions underpinning autism.

Indexing (document details)
Advisor: Hu, Valerie W.
Commitee: Vanderhoek, Jack Y.
School: The George Washington University
Department: Genomics and Bioinformatics
School Location: United States -- District of Columbia
Source: MAI 47/03M, Masters Abstracts International
Subjects: Molecular biology, Genetics, Bioinformatics
Keywords: Autism, Epigenetic, Lymphoblastoid cell lines, Microarrays, Noncoding RNA, miRNA
Publication Number: 1460204
ISBN: 978-0-549-92769-3
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