High throughput transcriptome analysis of lipid metabolism in Syrian hamster liver in absence of an annotated genome

Episode von Medizin - Open Access LMU - Teil 21/22 von Ludwig-Maximilians-Universität München · 1. Januar 2013

Background: Whole transcriptome analyses are an essential tool for understanding disease mechanisms. Approaches based on next-generation sequencing provide fast and affordable data but rely on the availability of annotated genomes. However, there are many areas in biomedical research that require non-standard animal models for which genome information is not available. This includes the Syrian hamster Mesocricetus auratus as an important model for dyslipidaemia because it mirrors many aspects of human disease and pharmacological responses. We show that complementary use of two independent next generation sequencing technologies combined with mapping to multiple genome databases allows unambiguous transcript annotation and quantitative transcript imaging. We refer to this approach as ``triple match sequencing{''} (TMS). Results: Contigs assembled from a normalized Roche 454 hamster liver library comprising 1.2 million long reads were used to identify 10'800 unique transcripts based on homology to RefSeq database entries from human, mouse, and rat. For mRNA quantification we mapped 82 million SAGE tags (SOLiD) from the same RNA source to the annotated hamster liver transcriptome contigs. We compared the liver transcriptome of hamster with equivalent data from human, rat, minipig, and cynomolgus monkeys to highlight differential gene expression with focus on lipid metabolism. We identify a cluster of five genes functionally related to HDL metabolism that is expressed in human, cynomolgus, minipig, and hamster but lacking in rat as a non-responder species for lipid lowering drugs. Conclusions: The TMS approach is suited for fast and inexpensive transcript profiling in cells or tissues of species where a fully annotated genome is not available. The continuously growing number of well annotated reference genomes will further empower reliable transcript identification and thereby raise the utility of the method for any species of interest.

Weitere Episoden von „Medizin - Open Access LMU - Teil 21/22“

• A genotype-specific, randomized controlled behavioral intervention to improve the neuroemotional outcome of cardiac surgery: study protocol for a randomized controlled trial 1. Januar 2013
• A new web-based method for automated analysis of muscle histology 1. Januar 2013
• Acceptance of routine or case-based inquiry for intimate partner violence: a mixed method study 1. Januar 2013
• Activation of axonal Kv7 channels in human peripheral nerve by flupirtine but not placebo - therapeutic potential for peripheral neuropathies: results of a randomised controlled trial 1. Januar 2013
• Aequilibrium prudentis: on the necessity for ethics and policy studies in the scientific and technological education of medical professionals 1. Januar 2013
• An AUC-based permutation variable importance measure for random forests 1. Januar 2013
• Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum 1. Januar 2013
• `Burden to others' as a public concern in advanced cancer: a comparative survey in seven European countries 1. Januar 2013
• Characterization of in vivo chemoresistant human hepatocellular carcinoma cells with transendothelial differentiation capacities 1. Januar 2013
• Conscious Presence and Self Control as a measure of situational awareness in soldiers - A validation study 1. Januar 2013
• Contrast enhanced transesophageal echocardiography in patients with atrial fibrillation referred to electrical cardioversion improves atrial thrombus detection and may reduce associated thromboembolic events 1. Januar 2013
• Current experience with applying the GRADE approach to public health interventions: an empirical study 1. Januar 2013
• Current management of patients hospitalized with community-acquired pneumonia across Europe: outcomes from REACH 1. Januar 2013
• Diversity of the var gene family of Indonesian Plasmodium falciparum isolates 1. Januar 2013
• A comparative analysis of the properties of regulated promoter systems commonly used for recombinant gene expression in Escherichia coli 1. Januar 2013

Alle Episoden von Medizin - Open Access LMU - Teil 21/22 · Mehr Bildung-Podcasts