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Rat Genome Assemblies, Annotation, and Variant Repository

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Rat Genomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2018))

Abstract

The first and only published version of the rat reference genome sequence was RGSC3.1, accomplished by the Rat Genome Sequencing Project Consortium. Here we present the history of the community effort in the correction of sequence errors and filling missing gaps in the process of refining and providing researchers with a high-quality rat reference sequence. The genome assembly improvements, addition of different evidence resources over time, such as RNA-Seq data, and software development methodologies had a positive impact on the gene model annotations. Over the years we observed a great increase in the numbers of genes, protein coding sequences, predicted transcripts and transcript features. Before the sequencing of the rat genome was possible, first biochemical and next genomic markers like RAPD, AFLP, RFLP, and SSLP were fundamental in research studies involving cross-breeding between different rat strains, in finding the level of polymorphism, linkage mapping, and phylogeny. Linkage maps provide information on recombination rates, give insight into intra- and interspecies gene rearrangements, and help to identify Mendelian loci and Quantitative Trait Loci (QTL). In the 1990s many reports were published on the construction of rat linkage maps that incorporated increasing numbers of markers and facilitated the localization of disease loci. Current genetic monitoring and linkage mapping relies on single nucleotide polymorphisms (SNPs). The Rat Genome Database collects information on genetic variation from the worldwide community of rat researchers and provides tools for searching and retrieving these data. As of today we show details about almost 605 million variants coming from many studies in our Variant Visualizer tool.

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References

  1. Gibbs RA, Weinstock GM, Metzker ML, Muzny DM, Sodergren EJ, Scherer S et al (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428(6982):493–521

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Krzywinski M, Wallis J, Gösele C, Bosdet I, Chiu R, Graves T et al (2004) Integrated and sequence-ordered BAC- and YAC-based physical maps for the rat genome. Genome Res 14(4):766–779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kren V, Qi N, Krenova D, Zidek V, Sladká M, Jáchymová M, Míková B et al (2001) Y-chromosome transfer induces changes in blood pressure and blood lipids in SHR. Hypertension 37(4):1147–1152

    Article  CAS  PubMed  Google Scholar 

  5. Gibbs R, Weinstock G (2005) Upgrading the DNA sequence of the rat genome. White paper available at https://www.genome.gov/pages/research/sequencing/seqproposals/ratupgradeseq.pdf

  6. van Boxtel R, Cuppen E (2010) Rat traps: filling the toolbox for manipulating the rat genome. Genome Biol 11(9):217. https://doi.org/10.1186/gb-2010-11-9-217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Prokop JW, Underwood AC, Turner ME, Miller N, Pietrzak D, Scott S et al (2013) Analysis of Sry duplications on the Rattus norvegicus Y-chromosome. BMC Genomics 14:792. https://doi.org/10.1186/1471-2164-14-792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rozen S, Warren WC, Weinstock G, O’Brien SJ, Gibbs RA, Richard K et al (2006) Sequencing and annotating new mammalian Y chromosomes. White paper available at https://www.genome.gov/pages/research/sequencing/seqproposals/ychromosomewp.pdf

  9. STAR Consortium, Saar K, Beck A, Bihoreau MT, Birney E, Brocklebank D et al (2008) SNP and haplotype mapping for genetic analysis in the rat. Nat Genet 40(5):560–566. https://doi.org/10.1038/ng.124

  10. Atanur SS, Birol I, Guryev V, Hirst M, Hummel O, Morrissey C et al (2010) The genome sequence of the spontaneously hypertensive rat: analysis and functional significance. Genome Res 20(6):791–803. https://doi.org/10.1101/gr.103499.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Simonis M, Atanur SS, Linsen S, Guryev V, Ruzius FP, Game L et al (2012) Genetic basis of transcriptome differences between the founder strains of the rat HXB/BXH recombinant inbred panel. Genome Biol 13(4):r31. https://doi.org/10.1186/gb-2012-13-4-r31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Guo X, Brenner M, Zhang X, Laragione T, Tai S, Li Y et al (2013) Whole-genome sequences of DA and F344 rats with different susceptibilities to arthritis, autoimmunity, inflammation and cancer. Genetics 194(4):1017–1028. https://doi.org/10.1534/genetics.113.153049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li R, Yu C, Li Y, Lam TW, Yiu SM, Kristiansen K et al (2009) SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25(15):1966–1967. https://doi.org/10.1093/bioinformatics/btp336

    Article  CAS  PubMed  Google Scholar 

  14. Li R, Zhu H, Ruan J, Qian W, Fang X, Shi Z et al (2010) De novo assembly of human genomes with massively parallel short read sequencing. Genome Res 20(2):265–272. https://doi.org/10.1101/gr.097261.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rat Genome Sequencing and Mapping Consortium, Baud A, Hermsen R, Guryev V, Stridh P, Graham D et al (2013) Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nat Genet 45(7):767–775. https://doi.org/10.1038/ng.2644

  16. Atanur SS, Diaz AG, Maratou K, Sarkis A, Rotival M, Game L et al (2013) Genome sequencing reveals loci under artificial selection that underlie disease phenotypes in the laboratory rat. Cell 154(3):691–703. https://doi.org/10.1016/j.cell.2013.06.040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Aitman TJ, Dong R, Vyse TJ, Norsworthy PJ, Johnson MD, Smith J et al (2006) Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439(7078):851–855

    Article  CAS  PubMed  Google Scholar 

  18. Thibaud-Nissen F, Souvorov A, Murphy T, DiCuccio M, Kitts P (2013) Eukaryotic genome annotation pipeline. In: The NCBI handbook, 2nd edn. National Center for Biotechnology Information, Bethesda. https://www.ncbi.nlm.nih.gov/books/NBK169439/

    Google Scholar 

  19. Yeh RF, Lim LP, Burge CB (2001) Computational inference of homologous gene structures in the human genome. Genome Res 11(5):803–816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Aken BL, Ayling S, Barrell D, Clarke L, Curwen V, Fairley S et al (2016) The Ensembl gene annotation system. Database (Oxford) 2016:baw093. https://doi.org/10.1093/database/baw093

    Article  CAS  Google Scholar 

  21. Birney E, Clamp M, Durbin R (2004) GeneWise and Genomewise. Genome Res 14(5):988–995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. National Center for Biotechnology Information (2005) US National Library of Medicine, Bethesda. http://www.ncbi.nlm.nih.gov. Accessed 1 Feb 2015

  23. Yates A, Akanni W, Amode MR, Barrell D, Billis K, Carvalho-Silva D et al (2016) Ensembl 2016. Nucleic Acids Res 44:D710–D716. https://doi.org/10.1093/nar/gkv1157

    Article  CAS  PubMed  Google Scholar 

  24. Buels R, Yao E, Diesh CM, Hayes RD, Munoz-Torres M, Helt G et al (2016) JBrowse: a dynamic web platform for genome visualization and analysis. Genome Biol 17:66. https://doi.org/10.1186/s13059-016-0924-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kumar D, Yadav AK, Jia X, Mulvenna J, Dash D (2015) Integrated transcriptomic-proteomic analysis using a proteogenomic workflow refines rat genome annotation. Mol Cell Proteomics 15(1):329–339. https://doi.org/10.1074/mcp.M114.047126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wu PY, Phan JH, Wang MD (2013) Assessing the impact of human genome annotation choice on RNA-seq expression estimates. BMC Bioinformatics 11:S8. https://doi.org/10.1186/1471-2105-14-S11-S8

    Article  Google Scholar 

  27. Serikawa T, Kuramoto T, Hilbert P, Mori M, Yamada J, Dubay CJ et al (1992) Rat gene mapping using PCR-analyzed microsatellites. Genetics 131(3):701–721

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Jacob HJ, Brown DM, Bunker RK, Daly MJ, Dzau VJ, Goodman A et al (1995) A genetic linkage map of the laboratory rat, Rattus norvegicus. Nat Genet 9(1):63–69

    Article  CAS  PubMed  Google Scholar 

  29. Steen RG, Kwitek-Black AE, Glenn C, Gullings-Handley J, Van Etten W, Atkinson OS et al (1999) A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat. Genome Res 9(6):AP1–AP8. Erratum in: Genome Res 1999 9(8):793

    CAS  PubMed  Google Scholar 

  30. Hutton JJ, Roderick TH (1970) Linkage analyses using biochemical variants in mice. 3. Linkage relationships of eleven biochemical markers. Biochem Genet 4(2):339–350

    Article  CAS  PubMed  Google Scholar 

  31. Moutier R, Toyama K, Charrier MF (1973) Biochemical polymorphism in the rat, Rattus norvegicus: genetic study of four markers. Biochem Genet 8(3):321–328

    Article  CAS  PubMed  Google Scholar 

  32. Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet 32(3):314–331

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Williams JG, Kubelik AR, Livak KJ, Rafalski JA, Tingey SV (1990) DNA polymorphisms amplified by arbitrary primers are useful as genetic markers. Nucleic Acids Res 18:6531–6535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bryda EC, Riley LK (2008) Multiplex microsatellite marker panels for genetic monitoring of common rat strains. J Am Assoc Lab Anim Sci 47(3):37–41

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Jacob HJ, Lindpaintner K, Lincoln SE, Kusumi K, Bunker RK, Mao YP et al (1991) Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell 67(1):213–224

    Article  CAS  PubMed  Google Scholar 

  36. Levan G, Szpirer J, Szpirer C, Klinga K, Hanson C, Islam MQ (1991) The gene map of the Norway rat (Rattus norvegicus) and comparative mapping with mouse and man. Genomics 10:699–718

    Article  CAS  PubMed  Google Scholar 

  37. Bihoreau M-T, Sebag-Montefiore L, Godfrey RF, Wallis RH, Brown JH, Danoy PA et al (1997) A high-resolution consensus linkage map of the rat, integrating radiation hybrid and genetic maps. Genomics 75:57–69

    Article  Google Scholar 

  38. Brown DM, Matise TC, Koike G, Simon JS, Winer ES, Zangen S et al (1998) An integrated genetic linkage map of the laboratory rat. Mamm Genome 9(7):521–530

    Article  CAS  PubMed  Google Scholar 

  39. Jensen-Seaman MI, Furey TS, Payseur BA, Lu Y, Roskin KM, Chen CF et al (2004) Comparative recombination rates in the rat, mouse, and human genomes. Genome Res 14(4):528–538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Littrell J, Tsaih SW, Baud A, Rastas P, Solberg-Woods L, Flister MJ (2018) A high-resolution genetic map for the laboratory rat. G3 (Bethesda) 8(7):2241–2248

    Article  CAS  Google Scholar 

  41. Bhérer C, Campbell CL, Auton A (2017) Refined genetic maps reveal sexual dimorphism in human meiotic recombination at multiple scales. Nat Commun 8:14994

    Article  PubMed  PubMed Central  Google Scholar 

  42. Morgan AP, Gatti DM, Najarian ML, Keane TM, Galante RJ, Pack AI et al (2017) Structural variation shapes the landscape of recombination in mouse. Genetics 206:603–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ulirsch JC, Nandakumar SK, Wang L, Giani FC, Zhang X, Rogov P et al (2016) Systematic functional dissection of common genetic variation affecting red blood cell traits. Cell 165(6):1530–1545. https://doi.org/10.1016/j.cell.2016.04.048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S et al (2014) Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet 46(11):1173–1186. https://doi.org/10.1038/ng.3097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Shimoyama M, De Pons J, Hayman GT, Laulederkind SJ, Liu W, Nigam R et al (2015) The Rat Genome Database 2015: genomic, phenotypic and environmental variations and disease. Nucleic Acids Res 43(Database issue):D743–D750

    Article  CAS  PubMed  Google Scholar 

  46. Twigger SN, Pruitt KD, Fernández-Suárez XM, Karolchik D, Worley KC, Maglott DR et al (2008) What everybody should know about the rat genome and its online resources. Nat Genet 40(5):523–527. https://doi.org/10.1038/ng0508-523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hermsen R, de Ligt J, Spee W, Blokzijl F, Schäfer S, Adami E et al (2015) Genomic landscape of rat strain and substrain variation. BMC Genomics 16:357. https://doi.org/10.1186/s12864-015-1594-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. She R, Jarosz DF (2018) Mapping causal variants with single-nucleotide resolution reveals biochemical drivers of phenotypic change. Cell 172(3):478–490. https://doi.org/10.1016/j.cell.2017.12.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Festing MF, Bender K (1984) Genetic relationships between inbred strains of rats. An analysis based on genetic markers at 28 biochemical loci. Genet Res 44(3):271–281

    Article  CAS  PubMed  Google Scholar 

  50. Canzian F, Ushijima T, Pascale R, Sugimura T, Dragani TA, Nagao M (1995) Construction of a phylogenetic tree for inbred strains of rat by arbitrarily primed polymerase chain reaction (AP-PCR). Mamm Genome 6(4):231–235

    Article  CAS  PubMed  Google Scholar 

  51. Canzian F (1997) Phylogenetics of the laboratory rat Rattus norvegicus. Genome Res 7(3):262–267

    Article  CAS  PubMed  Google Scholar 

  52. Thomas MA, Chen CF, Jensen-Seaman MI, Tonellato PJ, Twigger SN (2003) Phylogenetics of rat inbred strains. Mamm Genome 14(1):61–64

    Article  PubMed  Google Scholar 

  53. Mashimo T, Voigt B, Tsurumi T, Naoi K, Nakanishi S, Yamasaki K et al (2006) A set of highly informative rat simple sequence length polymorphism (SSLP) markers and genetically defined rat strains. BMC Genet 7:19

    Article  PubMed  PubMed Central  Google Scholar 

  54. Nijman IJ, Kuipers S, Verheul M, Guryev V, Cuppen E (2008) A genome-wide SNP panel for mapping and association studies in the rat. BMC Genomics 9:95. https://doi.org/10.1186/1471-2164-9-95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Battula KK, Nappanveettil G, Nakanishi S, Kuramoto T, Friedman JM, Kalashikam RR (2015) Genetic relatedness of WNIN and WNIN/Ob with major rat strains in biomedical research. Biochem Genet 53(4–6):132–140. https://doi.org/10.1007/s10528-015-9679-8

    Article  CAS  PubMed  Google Scholar 

  56. Smits BM, Guryev V, Zeegers D, Wedekind D, Hedrich HJ, Cuppen E (2005) Efficient single nucleotide polymorphism discovery in laboratory rat strains using wild rat-derived SNP candidates. BMC Genomics 6:170

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ren Y (2016) Multi-omics analysis of a rat model of aerobic exercise capacity and metabolic fitness. PhD dissertation, University of Michigan, Michigan

    Google Scholar 

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Correspondence to Monika Tutaj .

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Tutaj, M., Smith, J.R., Bolton, E.R. (2019). Rat Genome Assemblies, Annotation, and Variant Repository. In: Hayman, G., Smith, J., Dwinell, M., Shimoyama, M. (eds) Rat Genomics. Methods in Molecular Biology, vol 2018. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9581-3_2

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  • DOI: https://doi.org/10.1007/978-1-4939-9581-3_2

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