whole transcriptome sequencing reveals gene expression and splicing differences in brain regions affected by alzheimers disease全转录组测序揭示基因表达和拼接不同的大脑区域受到阿尔茨海默氏症的影响.pdfVIP

Whole Transcriptome Sequencing Reveals Gene Expression and Splicing Differences in Brain Regions Affected by Alzheimer’s Disease 1,2 3 1,2,3 1 Natalie A. Twine , Karolina Janitz , Marc R. Wilkins , Michal Janitz * 1 School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia, 2 New South Wales Systems Biology Initiative, University of New South Wales, Sydney, New South Wales, Australia, 3 Ramaciotti Centre for Gene Function Analysis, University of New South Wales, Sydney, New South Wales, Australia Abstract Recent studies strongly indicate that aberrations in the control of gene expression might contribute to the initiation and progression of Alzheimer’s disease (AD). In particular, alternative splicing has been suggested to play a role in spontaneous cases of AD. Previous transcriptome profiling of AD models and patient samples using microarrays delivered conflicting results. This study provides, for the first time, transcriptomic analysis for distinct regions of the AD brain using RNA-Seq next- generation sequencing technology. Illumina RNA-Seq analysis was used to survey transcriptome profiles from total brain, frontal and temporal lobe of healthy and AD post-mortem tissue. We quantified gene expression levels, splicing isoforms and alternative transcript start sites. Gene Ontology term enrichment analysis revealed an overrepresentation of genes associated with a neuron’s cytological structure and synapse function in AD brain samples. Analysis of the temporal lobe with the Cufflinks tool revealed that transcriptional isoforms of the apolipoprotein E gene, APOE-001, -002 and -005, are under the control of different promoters in normal and AD brain tissue. We also obse