Comparative analyses of Campylobacter concisusstrains reveal the genome of the reference strain BAA-1457 is not representative of the species

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that significant genotypic heterogeneity exists among <it>Campylobacter concisus </it>strains. Recently, the genome of <it>C. concisus </it>UNSWCD, isolated from a patient with Crohn's disease, was sequenced.</p> <p>Results</p> <p>In this study, comparative analyses were performed between strain UNSWCD and BAA-1457, isolated from a patient with acute gastroenteritis. Searches between <it>C. concisus </it>UNSWCD and BAA-1457 showed that 76% of genes were homologues, whereas those between <it>C. jejuni </it>strains showed 90-91% to be homologues, indicating substantial variation exists within these two <it>C. concisus </it>genomes. More specific bidirectional homology searches identified 1593 genes that are shared between these strains, and 115 and 281 genes unique to UNSWCD and BAA-1457, respectively. Significantly, differences in the type of flagellin glycosylation pathways between the two strains were identified and confirmed by PCR. The protein profiles of UNSWCD, BAA-1457 and a further six strains of <it>C. concisus </it>were compared and analyzed bioinformatically, and this differentiated the strains into four clades. BAA-1457 was found to be highly divergent (average similarity: 56.8%) from the other seven strains (mean average similarity ± standard deviation: 64.7 ± 1.7%). Furthermore, searches for homologues of the 1593 proteins found to be common between UNSWCD and BAA-1457 were conducted against all available bacterial genomes, and 18 proteins were found to be unique to <it>C. concisus</it>, of which 6 were predicted to be secreted, and may represent good markers for detection of this species.</p> <p>Conclusions</p> <p>This study has elucidated several features that may be responsible for the heterogeneity that exists among <it>C. concisus </it>strains, and has determined that the strain BAA-1457 is genetically atypical to other <it>C. concisus </it>strains and is not a good candidate reference strain.</p

Whole Transcriptome Sequencing Reveals Gene Expression and Splicing Differences in Brain Regions Affected by Alzheimer's Disease

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 observed differing expression levels of APOE-001 and -002 splice variants in the AD temporal lobe. Our results indicate that alternative splicing and promoter usage of the APOE gene in AD brain tissue might reflect the progression of neurodegeneration