What everybody should know about the rat genome and its online resources

Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA.
Nature Genetics (Impact Factor: 29.35). 06/2008; 40(5):523-7. DOI: 10.1038/ng0508-523
Source: PubMed


It has been four years since the original publication of the draft sequence of the rat genome. Five groups are now working together to assemble, annotate and release an updated version of the rat genome. As the prevailing model for physiology, complex disease and pharmacological studies, there is an acute need for the rat's genomic resources to keep pace with the rat's prominence in the laboratory. In this commentary, we describe the current status of the rat genome sequence and the plans for its impending 'upgrade'. We then cover the key online resources providing access to the rat genome, including the new SNP views at Ensembl, the RefSeq and Genes databases at the US National Center for Biotechnology Information, Genome Browser at the University of California Santa Cruz and the disease portals for cardiovascular disease and obesity at the Rat Genome Database.

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    • "; Rat Genome Sequencing Project Consortium 2004; Chimpanzee Sequencing and Analysis Consortium 2005; Levy et al. 2007; Rhesus Macaque Genome Sequencing and Analysis Consortium 2007; Bentley et al. 2008; Twigger et al. 2008; Wang et al. 2008; Li et al. 2010; Gnerre et al. 2011; Kim et al. 2011; Lindblad-Toh et al. 2011; Locke et al. 2011; Xu et al. 2011; Yan et al. 2011; Perry et al. 2012; Prüfer et al. 2012; Scally et al. 2012 "
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    ABSTRACT: Genome studies of mammals in the superorder Euarchontoglires (a clade that comprises the orders Primates, Dermoptera, Scandentia, Rodentia, and Lagomorpha) are important for understanding the biological features of humans, particularly studies of medical model animals such as macaques and mice. Furthermore, the dynamic eco-evolutionary signatures of Euarchontoglires genomes may be discovered because many species in this clade are characterized by their successful adaptive radiation to various ecological niches. In the present study, we investigated the evolutionary trajectory of bitter taste receptor genes (TAS2Rs) in 28 Euarchontoglires species based on homology searches of 39 whole-genome assemblies. The Euarchontoglires species possessed variable numbers of intact TAS2Rs, which ranged from 16 to 40, and their last common ancestor had at least 26 intact TAS2Rs. The gene tree showed that there have been at least 7 lineage-specific events involving massive gene duplications. Gene duplications were particularly evident in the ancestral branches of anthropoids (the anthropoid cluster), which may have promoted the adaptive evolution of anthropoid characteristics, such as a trade-off between olfaction and other senses and the development of herbivorous characteristics. Subsequent whole-gene deletions of anthropoid cluster TAS2Rs in hominoid species suggest ongoing ectopic homologous recombination in the anthropoid cluster. These findings provide insights into the roles of adaptive sensory evolution in various ecological niches and important clues related to the molecular mechanisms that underlie taste diversity in Euarchontoglires mammalian species, including humans.
    Molecular Biology and Evolution 04/2014; 31(8). DOI:10.1093/molbev/msu144 · 9.11 Impact Factor
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    • "RNA-Seq offers the potential for de novo definition of intron-exon boundaries, 5′- and 3′-untranslated regions, splice variants, single nucleotide polymorphisms (SNPs), and potentially new transcripts at a highly accurate level of quantitation, all of which are crucial for the analysis of differential gene expression [3], [4], [5]. The laboratory rat is an important experimental animal model for the study of chemically-induced diseases but RNA-Seq studies of rat tissues [6], [7], [8], [9], [10], [11] are still rather limited in part because its complete genomic sequence and annotation are still being refined [12], [13]. Published rat transcript profiling studies have focused on effects in the ageing cerebral cortex [10], neurons in the nucleus accumbens [6], the hippocampus of alcohol-addicted rats [7], functional compartments in the rat placentation site [9], the ventricular myocardium from SHR rats, [8] and kidneys from aristolochic acid exposed animals [14]. "
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    ABSTRACT: Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1), a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG) than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL). Paired-end reads were mapped to the rat genome (Rn4) with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005) compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's) on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c. We find the rat transcriptome contains many previously unidentified, AFB1-responsive exons and transcripts supporting RNA-Seq's capabilities to provide new insights into AFB1-mediated gene expression leading to hepatocellular carcinoma.
    PLoS ONE 04/2013; 8(4):e61768. DOI:10.1371/journal.pone.0061768 · 3.23 Impact Factor
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    • "Rat has been the traditional model for the study of ventilatory response to hypoxia (Powell et al., 2000). Accompanied by its resolved genome and a broad base of supporting information regarding genetic polymorphism, rat represents a supreme model for the study of genetic background effect in respect to hypoxia (Twigger et al., 2008). Previous data showed that among the inbred rat strains, BN, but not SS, is robust against hypoxia (Hodges et al., 2002). "
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    ABSTRACT: Genetic background of an individual can drastically influence an organism's response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN), Dahl salt-sensitive (SS) rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome substitution methodology, this genome-based physiological predisposition could not be traced back to distinct quantitative trait loci. Upon the completion and public data availabil-ity of PhysGen SS-BN consomic (CS) rat platform, I employed systems biology approach attempting to further our understanding of the molecular basis of genetic background effect in light of hypoxia response. I analyzed the physiological screening data of 22 CS rat strains under normoxia and 2-weeks of hypoxia, and cross-compared them to the parental strains. The analyses showed that SS-9 BN and SS-18 BN represent the most hypoxia-resistant CS strains with phenotype similar to BN, whereas SS-6 BN and SS-Y BN segregated to the direc-tion of SS. A meta-analysis on the transcriptomic profiles of these CS rat strains under hypoxia treatment showed that although polymorphisms on the substituted BN chromo-somes could be directly involved in hypoxia resistance, this seems to be embedded in a more complex trans-chromosomal genetic regulatory network. Via information theory based modeling approach, this hypoxia relevant core genetic network was reverse engi-neered. Network analyses showed that the protective effects of BN chromosome 9 and 18 were reflected by a balanced activation of this core network centering on physiological homeostasis. Presumably, it is the system robustness constituted on such differential net-work activation that acts as hypoxia response modifier. Understanding of the intrinsic link between the individual genetic background and the network robustness will set a basis in the current scientific efforts toward personalized medicine.
    Frontiers in Genetics 10/2012; 3. DOI:10.3389/fgene.2012.00208
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