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Sequencing of the Rat Genome and Databases

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Rat Genomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 597))

Abstract

The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing and annotation of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. With the genome sequence in place, there is the prospect of not only linking the extensive literature of mechanistic and pharmacological studies in the rat to its genome, but by using comparative genomics to other organisms as well. Genome-wide association studies (GWAS) in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains challenging.

The explosion of genomic tools and sequence over the last decade has created a wealth of data. Along with the data has arisen a need to manage it and to make it usable to scientists with a wide-range of research interests. This chapter is designed to overview the existing sequence and its utility, as well as provide a glimpse of some of the databases and bioinformatic tools available to the investigator.

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References

  1. Jacob HJ (1999) Functional genomics and rat models. Genome Res 9:1013–1016

    Article  CAS  PubMed  Google Scholar 

  2. Steen RG, Kwitek-Black AE, Glenn C, Gullings-Handley J, Van Etten W, Atkinson OS, Appel D, Twigger S, Muir M, Mull T, Granados M, Kissebah M, Russo K, Crane R, Popp M, Peden M, Matise T, Brown DM, Lu J, Kingsmore S, Tonellato PJ, Rozen S, Slonim D, Young P, Jacob HJ (1999) A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat. Genome Res 9:AP1-8, insert

    Google Scholar 

  3. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S, Scott G, Steffen D, Worley KC, Burch PE, Okwuonu G, Hines S, Lewis L, DeRamo C, Delgado O, Dugan-Rocha S, Miner G, Morgan M, Hawes A, Gill R, Celera, Holt RA, Adams MD, Amanatides PG, Baden-Tillson H, Barnstead M, Chin S, Evans CA, Ferriera S, Fosler C, Glodek A, Gu Z, Jennings D, Kraft CL, Nguyen T, Pfannkoch CM, Sitter C, Sutton GG, Venter JC, Woodage T, Smith D, Lee HM, Gustafson E, Cahill P, Kana A, Doucette-Stamm L, Weinstock K, Fechtel K, Weiss RB, Dunn DM, Green ED, Blakesley RW, Bouffard GG, De Jong PJ, 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 CM, Shetty J, Shatsman S, Geer K, Chen Y, Abramzon S, Nierman WC, Havlak PH, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Li B, Liu Y, Qin X, Cawley S, Cooney AJ, D’Souza LM, Martin K, Wu JQ, Gonzalez-Garay ML, Jackson AR, Kalafus KJ, McLeod MP, Milosavljevic A, Virk D, Volkov A, Wheeler DA, Zhang Z, Bailey JA, Eichler EE, Tuzun E, Birney E, Mongin E, Ureta-Vidal A, Woodwark C, Zdobnov E, Bork P, Suyama M, Torrents D, Alexandersson M, Trask BJ, Young JM, Huang H, Wang H, Xing H, Daniels S, Gietzen D, Schmidt J, Stevens K, Vitt U, Wingrove J, Camara F, Mar Alba M, Abril JF, Guigo R, Smit A, Dubchak I, Rubin EM, Couronne O, Poliakov A, Hubner N, Ganten D, Goesele C, Hummel O, Kreitler T, Lee YA, Monti J, Schulz H, Zimdahl H, Himmelbauer H, Lehrach H, Jacob HJ, Bromberg S, Gullings-Handley J, Jensen-Seaman MI, Kwitek AE, Lazar J, Pasko D, Tonellato PJ, Twigger S, Ponting CP, Duarte JM, Rice S, Goodstadt L, Beatson SA, Emes RD, Winter EE, Webber C, Brandt P, Nyakatura G, Adetobi M, Chiaromonte F, Elnitski L, Eswara P, Hardison RC, Hou M, Kolbe D, Makova K, Miller W, Nekrutenko A, Riemer C, Schwartz S, Taylor J, Yang S, Zhang Y, Lindpaintner K, Andrews TD, Caccamo M, Clamp M, Clarke L, Curwen V, Durbin R, Eyras E, Searle SM, Cooper GM, Batzoglou S, Brudno M, Sidow A, Stone EA, Payseur BA, Bourque G, Lopez-Otin C, Puente XS, Chakrabarti K, Chatterji S, Dewey C, Pachter L, Bray N, Yap VB, Caspi A, Tesler G, Pevzner PA, Haussler D, Roskin KM, Baertsch R, Clawson H, Furey TS, Hinrichs AS, Karolchik D, Kent WJ, Rosenbloom KR, Trumbower H, Weirauch M, Cooper DN, Stenson PD, Ma B, Brent M, Arumugam M, Shteynberg D, Copley RR, Taylor MS, Riethman H, Mudunuri U, Peterson J, Guyer M, Felsenfeld A, Old S, Mockrin S, Collins F (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428:493–521

    Article  CAS  PubMed  Google Scholar 

  4. Havlak P, Chen R, Durbin KJ, Egan A, Ren Y, Song XZ, Weinstock GM, Gibbs RA (2004) The Atlas genome assembly system. Genome Res 14:721–732

    Article  CAS  PubMed  Google Scholar 

  5. Worley KC, Weinstock GM, Gibbs RA (2008) Rats in the genomic era. Physiol Genomics 32:273–282

    CAS  PubMed  Google Scholar 

  6. Hubbard TJ, Aken BL, Ayling S, Ballester B, Beal K, Bragin E, Brent S, Chen Y, Clapham P, Clarke L, Coates G, Fairley S, Fitzgerald S, Fernandez-Banet J, Gordon L, Graf S, Haider S, Hammond M, Holland R, Howe K, Jenkinson A, Johnson N, Kahari A, Keefe D, Keenan S, Kinsella R, Kokocinski F, Kulesha E, Lawson D, Longden I, Megy K, Meidl P, Overduin B, Parker A, Pritchard B, Rios D, Schuster M, Slater G, Smedley D, Spooner W, Spudich G, Trevanion S, Vilella A, Vogel J, White S, Wilder S, Zadissa A, Birney E, Cunningham F, Curwen V, Durbin R, Fernandez-Suarez XM, Herrero J, Kasprzyk A, Proctor G, Smith J, Searle S, Flicek P (2009) Ensembl 2009. Nucleic Acids Res 37:D690–D697

    Article  CAS  PubMed  Google Scholar 

  7. Sayers EW, Barrett T, Benson DA, Bryant SH, Canese K, Chetvernin V, Church DM, DiCuccio M, Edgar R, Federhen S, Feolo M, Geer LY, Helmberg W, Kapustin Y, Landsman D, Lipman DJ, Madden TL, Maglott DR, Miller V, Mizrachi I, Ostell J, Pruitt KD, Schuler GD, Sequeira E, Sherry ST, Shumway M, Sirotkin K, Souvorov A, Starchenko G, Tatusova TA, Wagner L, Yaschenko E, Ye J (2009) Database resources of the National Center for Biotechnology Information. Nucleic Acids Res 37:D5–D15

    Article  CAS  PubMed  Google Scholar 

  8. Dwinell MR, Worthey EA, Shimoyama M, Bakir-Gungor B, DePons J, Laulederkind S, Lowry T, Nigram R, Petri V, Smith J, Stoddard A, Twigger SN, Jacob HJ (2009) The Rat Genome Database 2009: variation, ontologies and pathways. Nucleic Acids Res 37:D744–D749

    Article  CAS  PubMed  Google Scholar 

  9. Curwen V, Eyras E, Andrews TD, Clarke L, Mongin E, Searle SM, Clamp M (2004) The Ensembl automatic gene annotation system. Genome Res 14:942–950

    Article  CAS  PubMed  Google Scholar 

  10. Pruitt KD, Tatusova T, Klimke W, Maglott DR (2009) NCBI Reference Sequences: current status, policy and new initiatives. Nucleic Acids Res 37:D32–D36

    Article  CAS  PubMed  Google Scholar 

  11. Yeh RF, Lim LP, Burge CB (2001) Compu­tational inference of homologous gene structures in the human genome. Genome Res 11:803–816

    Article  CAS  PubMed  Google Scholar 

  12. Smits BM, Cuppen E (2006) Rats go genomic. Genome Biol 7:306

    Article  PubMed  Google Scholar 

  13. Saar K, Beck A, Bihoreau MT, Birney E, Brocklebank D, Chen Y, Cuppen E, Demonchy S, Dopazo J, Flicek P, Foglio M, Fujiyama A, Gut IG, Gauguier D, Guigo R, Guryev V, Heinig M, Hummel O, Jahn N, Klages S, Kren V, Kube M, Kuhl H, Kuramoto T, Kuroki Y, Lechner D, Lee YA, Lopez-Bigas N, Lathrop GM, Mashimo T, Medina I, Mott R, Patone G, Perrier-Cornet JA, Platzer M, Pravenec M, Reinhardt R, Sakaki Y, Schilhabel M, Schulz H, Serikawa T, Shikhagaie M, Tatsumoto S, Taudien S, Toyoda A, Voigt B, Zelenika D, Zimdahl H, Hubner N (2008) SNP and haplotype mapping for genetic analysis in the rat. Nat Genet 40:560–566

    Article  CAS  PubMed  Google Scholar 

  14. Hammond MP, Birney E (2004) Genome information resources – developments at Ensembl. Trends Genet 20:268–272

    Article  CAS  PubMed  Google Scholar 

  15. Bailey JA, Eichler EE (2006) Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet 7:552–564

    Article  CAS  PubMed  Google Scholar 

  16. Lin CH, Li LH, Ho SF, Chuang TP, Wu JY, Chen YT, Fann CS (2008) A large-scale survey of genetic copy number variations among Han Chinese residing in Taiwan. BMC Genet 9:92

    Article  PubMed  Google Scholar 

  17. Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N, Redon R, Bird CP, de Grassi A, Lee C, Tyler-Smith C, Carter N, Scherer SW, Tavare S, Deloukas P, Hurles ME, Dermitzakis ET (2007) Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315:848–853

    Article  CAS  PubMed  Google Scholar 

  18. Cahan P, Li Y, Izumi M, Graubert TA (2009) The impact of copy number variation on local gene expression in mouse hematopoietic stem and progenitor cells. Nat Genet 41:430–437

    Article  CAS  PubMed  Google Scholar 

  19. Henrichsen CN, Vinckenbosch N, Zollner S, Chaignat E, Pradervand S, Schutz F, Ruedi M, Kaessmann H, Reymond A (2009) Segmental copy number variation shapes tissue transcriptomes. Nat Genet 41:424–429

    Article  CAS  PubMed  Google Scholar 

  20. Guryev V, Berezikov E, Malik R, Plasterk RH, Cuppen E (2004) Single nucleotide polymorphisms associated with rat expressed sequences. Genome Res 14:1438–1443

    Article  CAS  PubMed  Google Scholar 

  21. Stein LD, Mungall C, Shu S, Caudy M, Mangone M, Day A, Nickerson E, Stajich JE, Harris TW, Arva A, Lewis S (2002) The generic genome browser: a building block for a model organism system database. Genome Res 12:1599–1610

    Article  CAS  PubMed  Google Scholar 

  22. Kuhn RM, Karolchik D, Zweig AS, Wang T, Smith KE, Rosenbloom KR, Rhead B, Raney BJ, Pohl A, Pheasant M, Meyer L, Hsu F, Hinrichs AS, Harte RA, Giardine B, Fujita P, Diekhans M, Dreszer T, Clawson H, Barber GP, Haussler D, Kent WJ (2009) The UCSC Genome Browser Database: update 2009. Nucleic Acids Res 37:D755–D761

    Article  CAS  PubMed  Google Scholar 

  23. Shendure JA, Porreca GJ, Church GM (2008) Overview of DNA sequencing strategies. Curr Protoc Mol Biol. Chapter 7, Unit 7 1

    Google Scholar 

  24. Pravenec M, Klir P, Kren V, Zicha J, Kunes J (1989) An analysis of spontaneous hypertension in spontaneously hypertensive rats by means of new recombinant inbred strains. J Hypertens 7:217–221

    Article  CAS  PubMed  Google Scholar 

  25. Stein LD (2008) Towards a cyberinfrastructure for the biological sciences: progress, visions and challenges. Nat Rev Genet 9:678–688

    Article  CAS  PubMed  Google Scholar 

  26. Stevens R, Goble CA, Bechhofer S (2000) Ontology-based knowledge representation for bioinformatics. Brief Bioinform 1:398–414

    Article  CAS  PubMed  Google Scholar 

  27. Shimoyama M, Petri V, Pasko D, Bromberg S, Wu W, Chen J, Nenasheva N, Kwitek A, Twigger S, Jacob H (2005) Using multiple ontologies to integrate complex biological data. Comp Funct Genomics 6:373–378

    Article  CAS  PubMed  Google Scholar 

  28. Hill DP, Smith B, McAndrews-Hill MS, Blake JA (2008) Gene Ontology annotations: what they mean and where they come from. BMC Bioinformatics 9(Suppl 5):S2

    Article  PubMed  Google Scholar 

  29. Barrell D, Dimmer E, Huntley RP, Binns D, O’Donovan C, Apweiler R (2009) The GOA database in 2009 – an integrated Gene Ontology Annotation resource. Nucleic Acids Res 37:D396–D403

    Article  CAS  PubMed  Google Scholar 

  30. Dowell RD, Jokerst RM, Day A, Eddy SR, Stein L (2001) The distributed annotation system. BMC Bioinformatics 2:7

    Article  CAS  PubMed  Google Scholar 

  31. Hubbard T, Andrews D, Caccamo M, Cameron G, Chen Y, Clamp M, Clarke L, Coates G, Cox T, Cunningham F, Curwen V, Cutts T, Down T, Durbin R, Fernandez-Suarez XM, Gilbert J, Hammond M, Herrero J, Hotz H, Howe K, Iyer V, Jekosch K, Kahari A, Kasprzyk A, Keefe D, Keenan S, Kokocinsci F, London D, Longden I, McVicker G, Melsopp C, Meidl P, Potter S, Proctor G, Rae M, Rios D, Schuster M, Searle S, Severin J, Slater G, Smedley D, Smith J, Spooner W, Stabenau A, Stalker J, Storey R, Trevanion S, Ureta-Vidal A, Vogel J, White S, Woodwark C, Birney E (2005) Ensembl 2005. Nucleic Acids Res 33:D447–D453

    Article  CAS  PubMed  Google Scholar 

  32. Smedley D, Haider S, Ballester B, Holland R, London D, Thorisson G, Kasprzyk A (2009) BioMart – biological queries made easy. BMC Genomics 10:22

    Article  PubMed  Google Scholar 

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Acknowledgments

This chapter is predicated on the existence of a rich set of interconnected rat data resources made compatible through collaboration, both formal and informal, between multiple data producing, development, and curation teams. We gratefully acknowledge the ongoing contributions of groups at UCSC, RGD, NCBI, and Ensembl and the authors of tools interfacing with these resources, to which this chapter provides a very brief introduction. In particular, we acknowledge the contributions from Kim Pruitt, Donna Maglott, and Garth Brown and teams at NCBI; Ewan Birney, Steve Searle, and Xosé Fernández-Suárez and their teams at Ensembl; and Jim Kent and team at UCSC. In addition, we acknowledge the ongoing support of rat genomics by Richard Gibbs, George Weinstock, and Kim Worley and their teams at BCM-HGSC.

Funding for the Rat Genome Database is provided by the National Heart Lung and Blood Institute grant (HL64541) to Howard J. Jacob.

Author information

Authors and Affiliations

  1. Human & Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Elizabeth A. Worthey & Alexander J. Stoddard

  2. Human & Molecular Genetics Center, Departments of Physiology and Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Howard J. Jacob

Authors
  1. Elizabeth A. Worthey
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  2. Alexander J. Stoddard
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  3. Howard J. Jacob
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Corresponding author

Correspondence to Howard J. Jacob .

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Editors and Affiliations

  1. ITERT-INSERM U643, CHU de Nantes, bd. Jean Monnet 30, Nantes, 44093, France

    Ignacio Anegon

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Worthey, E.A., Stoddard, A.J., Jacob, H.J. (2010). Sequencing of the Rat Genome and Databases. In: Anegon, I. (eds) Rat Genomics. Methods in Molecular Biology, vol 597. Humana Press. https://doi.org/10.1007/978-1-60327-389-3_3

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  • DOI: https://doi.org/10.1007/978-1-60327-389-3_3

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-388-6

  • Online ISBN: 978-1-60327-389-3

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