Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq analysis of alternative splicing events in duplicated genes of Arabidopsis thaliana indicates considerable qualitative and quantitative divergence

ABSTRACT: Divergence of alternative splicing in duplicated genes is investigated Three replicates of RNA-seq for Arabidopsis first true leaf tissue

ORGANISM(S): Arabidopsis thaliana

SUBMITTER: David Tack

PROVIDER: E-GEOD-57579 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcriptome analysis indicates considerable divergence in alternative splicing between duplicated genes in Arabidopsis thaliana.

Tack David C DC Pitchers William R WR Adams Keith L KL

Genetics 20141016 4

Gene and genome duplication events have created a large number of new genes in plants that can diverge by evolving new expression profiles and functions (neofunctionalization) or dividing extant ones (subfunctionalization). Alternative splicing (AS) generates multiple types of mRNA from a single type of pre-mRNA by differential intron splicing. It can result in new protein isoforms or downregulation of gene expression by transcript decay. Using RNA-seq, we investigated the degree to which altern ...[more]

PMID: 25326238

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Project description:Autism spectrum disorder (ASD) is a common, highly heritable neurodevelopmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an aetiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1 (also known as FOX1), and a module enriched for immune genes and glial markers. Using high-throughput RNA sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in the ASD brain. Moreover, using a published autism genome-wide association study (GWAS) data set, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic aetiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. To identify potential A2BP1-dependent differential splicing events in ASD brain, we performed high-throughput RNA sequencing (RNA-Seq) on three autism samples with significant downregulation of A2BP1 (average fold change by quantitative RT-PCR = 5.9) and three control samples with average A2BP1 levels. The list of potential A2BP1-depending differential splicing events in ASD is given in the Supplementary file linked at the foot of this record.

Dataset Information

RNA-seq analysis of alternative splicing events in duplicated genes of Arabidopsis thaliana indicates considerable qualitative and quantitative divergence

Publications

Transcriptome analysis indicates considerable divergence in alternative splicing between duplicated genes in Arabidopsis thaliana.

Similar Datasets

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