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Exploring Phenotypic Data at the Rat Genome Database
Publication Name:
Current Protocols in Bioinformatics
Unit Number:
UNITÂ 1.14
DOI:
10.1002/0471250953.bi0114s14
Online Posting Date:
July, 2006 Abstract
The laboratory rat, Rattus norvegicus, is an important model of human health and disease, and experimental findings in the rat have direct relevance to human-based research. The Rat Genome Database (RGD, http://rgd.mcw.edu) is a model-organism database that provides access to wide variety of curated rat data such as genes and their homologs, quantitative trait loci, phenotypes, comparative mapping, and genome analysis. We present an overview of the database followed by specific examples that can be used to gain experience in employing RGD to explore the wealth of functional data available for the rat. We show how to make associations with the genome and use comparative tools to link the rat with human and mouse in order to integrate results from these three species of critical biomedical importance.
Keywords: Rat; database; quantitative trait; ontology; comparative genomics; genome sequence
Table of Contents
- Unit Introduction
- Basic Protocol 1: Navigating the RGD Home Page
- Basic Protocol 2: Using the RGDx Search Functions
- Basic Protocol 3: Searching for Quantitative Trait Loci
- Basic Protocol 4: Using the RGD Genome Browser (GBrowse) to Find Functional Annotations
- Basic Protocol 5: Using VCMap to View Syntenic Regions in Rat and Mouse
- Commentary
- Literature Cited
- Figures
- Tables
Figures
-
Figure 1.14.1Overview of this unit indicating general routes for searching RGD based on the information at hand. -
Figure 1.14.2GD Home page and RGD Category list. This list shows the main categories of content available in RGD and provides hyperlinks to each section. -
Figure 1.14.3Intermediate results Web page. -
Figure 1.14.4Search result Web page. Shown here are 10 genes that satisfied the query protease AND inhibitor. -
Figure 1.14.5Ontology Browser Result. The highest level of the molecular function ontology is shown along with its 15 branches. -
Figure 1.14.6Ontology Report. The report page shows the definition of the term, a genome-wide image showing the locations all the genes annotated to that term and its descendants, and a list of those genes and homologs. -
Figure 1.14.7GViewer Results. All genes and QTL annotated to the searched terms or its descendants are shown on each chromosome. Overlapping QTL are merged into a single line. Clicking on an individual chromosome/gene/QTL will bring up a detailed image of that chromosome. -
Figure 1.14.8Detailed GViewer Image. Individual genes and QTL are shown. Clicking on the gene or QTL label will lead to the report page. Clicking on the bar will lead to a GBrowse view. -
Figure 1.14.9The object-specific query form for Rat QTLs. See Basic Protocol 3 for details. -
Figure 1.14.10The QTL query result page. The QTL search yields 9 records that match the given criteria. See Basic Protocol 3 for details. -
Figure 1.14.11The QTL report page for rat Blood Pressure QTL 7. See Basic Protocol 3 for details. -
Figure 1.14.12The front page of the RGD GBrowse genome browser. All of the items displayed on the front page are also accessible on succeeding pages. See Basic Protocol 4 for details. -
Figure 1.14.13A search for arthritis yields 191 regions on 19 different chromosomes. Chromosome 20 contains four QTLs, Aia1, Cia1, Pia21, and Ciaa1, and one gene, Ager, which are annotated to arthritis. See Basic Protocol 4 for details. -
Figure 1.14.14The GBrowse image of the area of chromosome 20 covered by the Pia21 QTL. See Basic Protocol 4 for details. -
Figure 1.14.15Menus in the tracks table can be expanded by clicking on the plus sign (+) to the left of the heading text, revealing boxes that can be checked to display or unchecked to hide objects in the detail view. See Basic Protocol 4 for details. -
Figure 1.14.16The detail view of rat Chr20:4200957..4300956 with tracks showing the homologous segment of mouse chromosome 17, all of the known and predicted genes in this area of the chromosome, the QTLs that span the area, the mammalian phenotype and disease ontology terms for the Ager gene, and the single-nucleotide polymorphisms that have been found in this region of the chromosome. See Basic Protocol 4 for details. -
Figure 1.14.17Basic comparative map for rat chromosome 10 showing the syntenic regions in mouse. The Marker Names dialog box is also shown (see Basic Protocol 5 for details). -
Figure 1.14.18Rat arthritis QTL aligned with the comparative map of rat chromosome 10 and syntenic regions in mouse. -
Figure 1.14.19Rat arthritis QTL aligned with rat chromosome 10 and syntenic regions in mouse. Mouse chromosome 11 is aligned with the mouse QTL map for chromosome 11 and the locations of selected arthritis QTL have been highlighted.
Literature Cited
| Literature Cited | |
| Ashburner, M., Ball, C.A., Blake, J.A., Botstein, D., Butler, H., Cherry, J.M., Davis, A.P., Dolinski, K., Dwight, S.S., Eppig, J.T., Harris, M.A., Hill, D.P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J.C., Richardson, J.E., Ringwald, M., Rubin, G.M., and Sherlock, G. 2000. Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25:25-29. | |
| de la Cruz, N., Bromberg, S., Pasko, D., Shimoyama, M., Twigger, S., Chen, J., Chen, C.F., Fan, C., Foote, C., Gopinath, G.R., Harris, G., Hughes, A., Ji, Y., Jin, W., Li, D., Mathis, J., Nenasheva, N., Nie, J., Nigam, R., Petri, V., Reilly, D., Wang, W., Wu, W., Zuniga-Meyer, A., Zhao, L., Kwitek, A., Tonellato, P., and Jacob, H. 2005. The Rat Genome Database (RGD): Developments towards a phenome database. Nucl. Acids Res. 33:D485-D491. | |
| Gibbs, R.A., Weinstock, G.M., Metzker, M.L., Muzny, D.M., Sodergren, E.J., Scherer, S., Scott, G., Steffen, D., Worley, K.C., Burch, P.E., Okwuonu, G., Hines, S., Lewis, L., DeRamo, C., Delgado, O., Dugan-Rocha, S., Miner, G., Morgan, M., Hawes, A., Gill, R., CeleraHolt, R.A., Adams, M.D., Amanatides, P.G., Baden-Tillson, H., Barnstead, M., Chin, S., Evans, C.A., Ferriera, S., Fosler, C., Glodek, A., Gu, Z., Jennings, D., Kraft, C.L., Nguyen, T., Pfannkoch, C.M., Sitter, C., Sutton, G.G., Venter, J.C., Woodage, T., Smith, D., Lee, H.M., Gustafson, E., Cahill, P., Kana, A., Doucette-Stamm, L., Weinstock, K., Fechtel, K., Weiss, R.B., Dunn, D.M., Green, E.D., Blakesley, R.W., Bouffard, G.G., De Jong, P.J., Osoegawa, K., Zhu, B., Marra, M., Schein, J., Bosdet, I., Fjell, C., Jones, S., Krzywinski, M., Mathewson, C., Siddiqui, A., Wye, N., McPherson, J., Zhao, S., Fraser, C.M., Shetty, J., Shatsman, S., Geer, K., Chen, Y., Abramzon, S., Nierman, W.C., Havlak, P.H., Chen, R., Durbin, K.J., Egan, A., Ren, Y., Song, X.Z., Li, B., Liu, Y., Qin, X., Cawley, S., Cooney, A.J., D'Souza, L.M., Martin, K., Wu, J.Q., Gonzalez-Garay, M.L., Jackson, A.R., Kalafus, K.J., McLeod, M.P., Milosavljevic, A., Virk, D., Volkov, A., Wheeler, D.A., Zhang, Z., Bailey, J.A., Eichler, E.E., Tuzun, E., Birney, E., Mongin, E., Ureta-Vidal, A., Woodwark, C., Zdobnov, E., Bork, P., Suyama, M., Torrents, D., Alexandersson, M., Trask, B.J., Young, J.M., Huang, H., Wang, H., Xing, H., Daniels, S., Gietzen, D., Schmidt, J., Stevens, K., Vitt, U., Wingrove, J., Camara, F., Mar Alba, M., Abril, J.F., Guigo, R., Smit, A., Dubchak, I., Rubin, E.M., Couronne, O., Poliakov, A., Hubner, N., Ganten, D., Goesele, C., Hummel, O., Kreitler, T., Lee, Y.A., Monti, J., Schulz, H., Zimdahl, H., Himmelbauer, H., Lehrach, H., Jacob, H.J., Bromberg, S., Gullings-Handley, J., Jensen-Seaman, M.I., Kwitek, A.E., Lazar, J., Pasko, D., Tonellato, P.J., Twigger, S., Ponting, C.P., Duarte, J.M., Rice, S., Goodstadt, L., Beatson, S.A., Emes, R.D., Winter, E.E., Webber, C., Brandt, P., Nyakatura, G., Adetobi, M., Chiaromonte, F., Elnitski, L., Eswara, P., Hardison, R.C., Hou, M., Kolbe, D., Makova, K., Miller, W., Nekrutenko, A., Riemer, C., Schwartz, S., Taylor, J., Yang, S., Zhang, Y., Lindpaintner, K., Andrews, T.D., Caccamo, M., Clamp, M., Clarke, L., Curwen, V., Durbin, R., Eyras, E., Searle, S.M., Cooper, G.M., Batzoglou, S., Brudno, M., Sidow, A., Stone, E.A., Payseur, B.A., Bourque, G., Lopez-Otin, C., Puente, X.S., Chakrabarti, K., Chatterji, S., Dewey, C., Pachter, L., Bray, N., Yap, V.B., Caspi, A., Tesler, G., Pevzner, P.A., Haussler, D., Roskin, K.M., Baertsch, R., Clawson, H., Furey, T.S., Hinrichs, A.S., Karolchik, D., Kent, W.J., Rosenbloom, K.R., Trumbower, H., Weirauch, M., Cooper, D.N., Stenson, P.D., Ma, B., Brent, M., Arumugam, M., Shteynberg, D., Copley, R.R., Taylor, M.S., Riethman, H., Mudunuri, U., Peterson, J., Guyer, M., Felsenfeld, A., Old, S., Mockrin, S., and Collins, F. 2004. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428:493-521. | |
| Kwitek, A.E., Tonellato, P.J., Chen, D., Gullings-Handley, J., Cheng, Y.S., Twigger, S., Scheetz, T.E., Casavant, T.L., Stoll, M., Nobrega, M.A., Shiozawa, M., Soares, M.B., Sheffield, V.C., and Jacob, H.J. 2001. Automated construction of high-density comparative maps between rat, human, and mouse. Genome Res. 11:1935-1943. | |
| Smith, C.L., Goldsmith, C.A., and Eppig, J.T. 2005. The Mammalian Phenotype Ontology as a tool for annotating, analyzing and comparing phenotypic information. Genome Biol. 6:R7. | |
| Stein, L.D., Mungall, C., Shu, S., Caudy, M., Mangone, M., Day, A., Nickerson, E., Stajich, J.E., Harris, T.W., Arva, A., and Lewis, S. 2002. The generic genome browser: A building block for a model organism system database. Genome Res. 12:1599-1610. | |
| Twigger, S.N., Nie, J., Ruotti, V., Yu, J., Chen, D., Li, D., Mathis, J., Narayanasamy, V., Gopinath, G.R., Pasko, D., Shimoyama, M., De La Cruz, N., Bromberg, S., Kwitek, A.E., Jacob, H.J., and Tonellato, P.J. 2004. Integrative genomics: In silico coupling of rat physiology and complex traits with mouse and human data. Genome Res. 14:651-660. | |
| Twigger, S.N., Pasko, D., Nie, J., Shimoyama, M., Bromberg, S., Campbell, D., Chen, J., Dela Cruz, N., Fan, C., Foote, C., Harris, G., Hickmann, B., Ji, Y., Jin, W., Li, D., Mathis, J., Nenasheva, N., Nigam, R., Petri, V., Reilly, D., Ruotti, V., Schauberger, E., Seiler, K., Slyper, R., Smith, J., Wang, W., Wu, W., Zhao, L., Zuniga-Meyer, A., Tonellato, P.J., Kwitek, A.E., and Jacob, H.J. 2005. Tools and strategies for physiological genomics: The rat genome database. Physiol. Genomics 23:246-256. | |
| Key References | |
| Twigger et al., 2005. See above. | |
| Provides an overview of how to utilize all the RGD data and tools in the areas of comparative genomics, expression analysis, positional cloning, and functional genomics. | |
| de la Cruz et al., 2005. See above. | |
| The Nucleic Acids Research annual database edition provides an overview of RGD. | |
| Internet Resources | |
| http://rgd.mcw.edu | |
| The main Rat Genome Database Web site | |
| http://rat.lab.nig.ac.jp/ | |
| RGD mirror site at the National Institute of Genetics in Japan. | |
| ftp://rgd.mcw.edu/pub/ | |
| FTP site to download flat files of RGD data including genes, QTLs, microsatellites (SSLPs), maps (genetic, radiation hybrid), strains, genome annotations, and sequence files. | |
| http://rgd.mcw.edu/RCF/ | |
| Rat Community Forum, online bulletin board for rat-related questions | |
| http://rgd.mcw.edu/newsletter/ | |
| Pied Piper newsletter, covering new developments in rat genetics and genomics, upcoming meetings, and a list of Web resources useful to rat researchers. | |
| http://rgd.mcw.edu/tools/diseases/disease_search.cgi | |
| Initial development of the disease portal concept, providing one-click access to annotations and genomic regions associated with medically important disease conditions. | |
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