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01.07.2008 | Original Article

Heterogeneous dysregulation of microRNAs across the autism spectrum

verfasst von: Kawther Abu-Elneel, Tsunglin Liu, Francesca S. Gazzaniga, Yuhei Nishimura, Dennis P. Wall, Daniel H. Geschwind, Kaiqin Lao, Kenneth S. Kosik

Erschienen in: Neurogenetics | Ausgabe 3/2008

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Abstract

microRNAs (miRNAs) are ~21 nt transcripts capable of regulating the expression of many mRNAs and are abundant in the brain. miRNAs have a role in several complex diseases including cancer as well as some neurological diseases such as Tourette’s syndrome and Fragile x syndrome. As a genetically complex disease, dysregulation of miRNA expression might be a feature of autism spectrum disorders (ASDs). Using multiplex quantitative polymerase chain reaction (PCR), we compared the expression of 466 human miRNAs from postmortem cerebellar cortex tissue of individuals with ASD (n = 13) and a control set of non-autistic cerebellar samples (n = 13). While most miRNAs levels showed little variation across all samples suggesting that autism does not induce global dysfunction of miRNA expression, some miRNAs among the autistic samples were expressed at significantly different levels compared to the mean control value. Twenty-eight miRNAs were expressed at significantly different levels compared to the non-autism control set in at least one of the autism samples. To validate the finding, we reversed the analysis and compared each non-autism control to a single mean value for each miRNA across all autism cases. In this analysis, the number of dysregulated miRNAs fell from 28 to 9 miRNAs. Among the predicted targets of dysregulated miRNAs are genes that are known genetic causes of autism such Neurexin and SHANK3. This study finds that altered miRNA expression levels are observed in postmortem cerebellar cortex from autism patients, a finding which suggests that dysregulation of miRNAs may contribute to autism spectrum phenotype.

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Titel: Heterogeneous dysregulation of microRNAs across the autism spectrum
verfasst von: Kawther Abu-Elneel
Tsunglin Liu
Francesca S. Gazzaniga
Yuhei Nishimura
Dennis P. Wall
Daniel H. Geschwind
Kaiqin Lao
Kenneth S. Kosik
Publikationsdatum: 01.07.2008
Verlag: Springer Berlin Heidelberg
Erschienen in: Neurogenetics / Ausgabe 3/2008
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-008-0133-5

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