Skip to main content
SpringerLink
Log in
Book cover

Nuclear pre-mRNA Processing in Plants pp 17–37Cite as

Analysis of Alternative Splicing in Plants with Bioinformatics Tools

  • Chapter

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 326))

Alternative splicing is a molecular mechanism utilized by a broad range of eukaryotes to extend the repertoire of functions encoded by single genes and to posttranscriptionally regulate gene expression. Recent analyses of expressed transcript sequences aligned to the complete genomes of Arabidopsis and rice indicate that alternative splicing in plants is prevalent and exhibits several features similar to other higher eukaryotes including mouse and human. This chapter reviews the computational strategies employed to study alternative splicing with bioinformatics tools and the recent findings from analyses performed on plants by applying such methods.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Akerman M, Mandel-Gutfreund Y (2006) Alternative splicing regulation at tandem 3′ splice sites. Nucleic Acids Res 34:23–31

    Article  PubMed  CAS  Google Scholar 

  • Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402

    Article  PubMed  CAS  Google Scholar 

  • Arabidopsis Genome Initiative (2000) Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408:796–815

    Article  Google Scholar 

  • Baker BS (1989) Sex in flies: the splice of life. Nature 340:521–524

    Article  PubMed  CAS  Google Scholar 

  • Black DL (2003) Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336

    Article  PubMed  CAS  Google Scholar 

  • Blencowe BJ (2006) Alternative splicing: new insights from global analyses. Cell 126:37–47

    Article  PubMed  CAS  Google Scholar 

  • Brett D, Pospisil H, Valcarcel J, Reich J, Bork P (2002) Alternative splicing and genome complexity. Nat Genet 30:29–30

    Article  PubMed  CAS  Google Scholar 

  • Campbell MA, Haas BJ, Hamilton JP, Mount SM, Buell CR (2006) Comprehensive analysis of alternative splicing in rice and comparative analyses with Arabidopsis. BMC Genomics 7:327

    Article  PubMed  Google Scholar 

  • Chern TM, van Nimwegen E, Kai C, Kawai J, Carninci P, Hayashizaki Y, Zavolan M (2006) A simple physical model predicts small exon length variations. PLoS Genet 2:e45

    Article  PubMed  Google Scholar 

  • Dong Q, Lawrence CJ, Schlueter SD, Wilkerson MD, Kurtz S, Lushbough C, Brendel V (2005) Comparative plant genomics resources at PlantGDB. Plant Physiol 139:610–618

    Article  PubMed  CAS  Google Scholar 

  • Eyras E, Caccamo M, Curwen V, Clamp M (2004) ESTGenes: alternative splicing from ESTs in Ensembl. Genome Res 14:976–987

    Article  PubMed  CAS  Google Scholar 

  • Florea L, Hartzell G, Zhang Z, Rubin GM, Miller W (1998) A computer program for aligning a cDNA sequence with a genomic DNA sequence. Genome Res 8:967–974

    PubMed  CAS  Google Scholar 

  • Goff SA, Ricke D, Lan TH, Presting G, Wang R, Dunn M, Glazebrook J, Sessions A, Oeller P, Varma H, Hadley D, Hutchison D, Martin C, Katagiri F, Lange BM, Moughamer T, Xia Y, Budworth P, Zhong J, Miguel T, Paszkowski U, Zhang S, Colbert M, Sun WL, Chen L, Cooper B, Park S, Wood TC, Mao L, Quail P, Wing R, Dean R, Yu Y, Zharkikh A, Shen R, Sahasrabudhe S, Thomas A, Cannings R, Gutin A, Pruss D, Reid J, Tavtigian S, Mitchell J, Eldredge G, Scholl T, Miller RM, Bhatnagar S, Adey N, Rubano T, Tusneem N, Robinson R, Feldhaus J, Macalma T, Oliphant A, Briggs S (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. japonica). Science 296:92–100

    Article  PubMed  CAS  Google Scholar 

  • Graveley BR (2001) Alternative splicing: increasing diversity in the proteomic world. Trends Genet 17:100–107

    Article  PubMed  CAS  Google Scholar 

  • Haas BJ, Volfovsky N, Town CD, Troukhan M, Alexandrov N, Feldmann KA, Flavell RB, White O, Salzberg SL (2002) Full-length messenger RNA sequences greatly improve genome annotation. Genome Biol 3:RESEARCH0029

    Google Scholar 

  • Haas BJ, Delcher AL, Mount SM, Wortman JR, Smith RK Jr, Hannick LI, Maiti R, Ronning CM, Rusch DB, Town CD, Salzberg SL, White O (2003) Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies. Nucleic Acids Res 31:5654–5666

    Article  PubMed  CAS  Google Scholar 

  • Haas BJ, Wortman JR, Ronning CM, Hannick LI, Smith RK Jr, Maiti R, Chan AP, Yu C, Farzad M, Wu D, White O, Town CD (2005) Complete reannotation of the Arabidopsis genome: methods, tools, protocols and the final release. BMC Biol 3:7

    Article  PubMed  Google Scholar 

  • Heber S, Alekseyev M, Sze SH, Tang H, Pevzner PA (2002) Splicing graphs and EST assembly problem. Bioinformatics 18 [Suppl 1]:S181–S188

    PubMed  Google Scholar 

  • Hiller M, Huse K, Szafranski K, Jahn N, Hampe J, Schreiber S, Backofen R, Platzer M (2004) Widespread occurrence of alternative splicing at NAGNAG acceptors contributes to proteome plasticity. Nat Genet 36:1255–1257

    Article  PubMed  CAS  Google Scholar 

  • Hiller M, Szafranski K, Backofen R, Platzer M (2006) Alternative splicing at NAGNAG acceptors: simply noise or noise and more? PLoS Genet 2: e207; author reply e208

    Article  PubMed  Google Scholar 

  • Holste D, Huo G, Tung V, Burge CB (2006) HOLLYWOOD: a comparative relational database of alternative splicing. Nucleic Acids Res 34:D56–62

    Article  PubMed  CAS  Google Scholar 

  • Huang X, Adams MD, Zhou H, Kerlavage AR (1997) A tool for analyzing and annotating genomic sequences. Genomics 46:37–45

    Article  PubMed  CAS  Google Scholar 

  • Iida K, Seki M, Sakurai T, Satou M, Akiyama K, Toyoda T, Konagaya A, Shinozaki K (2004) Genome-wide analysis of alternative pre-mRNA splicing in Arabidopsis thaliana based on full-length cDNA sequences. Nucleic Acids Res 32:5096–5103

    Article  PubMed  CAS  Google Scholar 

  • International Human Genome Sequencing Consortium (2004) Finishing the euchromatic sequence of the human genome. Nature 431:931–945

    Article  Google Scholar 

  • International Rice Genome Sequencing Project (2005) The map-based sequence of the rice genome. Nature 436:793–800

    Article  Google Scholar 

  • Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD, Santos R, Schadt EE, Stoughton R, Shoemaker DD (2003) Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 302:2141–2144

    Article  PubMed  CAS  Google Scholar 

  • Kan Z, Rouchka EC, Gish WR, States DJ (2001) Gene structure prediction and alternative splicing analysis using genomically aligned ESTs. Genome Res 11:889–900

    Article  PubMed  CAS  Google Scholar 

  • Kent WJ (2002) BLAT—the BLAST-like alignment tool. Genome Res 12:656–664

    PubMed  CAS  Google Scholar 

  • Kim E, Magen A, Ast G (2007a) Different levels of alternative splicing among eukaryotes. Nucleic Acids Res 35:125–131

    Article  PubMed  CAS  Google Scholar 

  • Kim H, Klein R, Majewski J, Ott J (2004) Estimating rates of alternative splicing in mammals and invertebrates. Nat Genet 36:915–916; author reply 916–917

    Article  PubMed  CAS  Google Scholar 

  • Kim N, Alekseyenko AV, Roy M, Lee C (2007b) The ASAP II database: analysis and comparative genomics of alternative splicing in 15 animal species. Nucleic Acids Res 35:D93–D98

    Article  PubMed  CAS  Google Scholar 

  • Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  PubMed  CAS  Google Scholar 

  • Lareau LF, Green RE, Bhatnagar RS, Brenner SE (2004) The evolving roles of alternative splicing. Curr Opin Struct Biol 14:273–282

    Article  PubMed  CAS  Google Scholar 

  • Lee C (2003) Generating consensus sequences from partial order multiple sequence alignment graphs. Bioinformatics 19:999–1008

    Article  PubMed  CAS  Google Scholar 

  • Lee C, Wang Q (2005) Bioinformatics analysis of alternative splicing. Brief Bioinform 6:23–33

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Lee Y, Kim B, Shin Y, Nam S, Kim P, Kim N, Chung WH, Kim J, Lee S (2007) ECgene: an alternative splicing database update. Nucleic Acids Res 35:D99–103

    Article  PubMed  CAS  Google Scholar 

  • Leipzig J, Pevzner P, Heber S (2004) The Alternative Splicing Gallery (ASG): bridging the gap between genome and transcriptome. Nucleic Acids Res 32:3977–3983

    Article  PubMed  CAS  Google Scholar 

  • Lewis BP, Green RE, Brenner SE (2003) Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc Natl Acad Sci USA 100:189–192

    Article  PubMed  CAS  Google Scholar 

  • Licatalosi DD, Darnell RB (2006) Splicing regulation in neurologic disease. Neuron 52:93–101

    Article  PubMed  CAS  Google Scholar 

  • Magen A, Ast G (2005) The importance of being divisible by three in alternative splicing. Nucleic Acids Res 33:5574–5582

    Article  PubMed  CAS  Google Scholar 

  • Malde K, Coward E, Jonassen I (2005) A graph based algorithm for generating EST consensus sequences. Bioinformatics 21:1371–1375

    Article  PubMed  CAS  Google Scholar 

  • Maniatis T, Tasic B (2002) Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418:236–243

    Article  PubMed  CAS  Google Scholar 

  • Modrek B, Lee C (2002) A genomic view of alternative splicing. Nat Genet 30:13–19

    Article  PubMed  CAS  Google Scholar 

  • Modrek B, Resch A, Grasso C, Lee C (2001) Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res 29:2850–2859

    Article  PubMed  CAS  Google Scholar 

  • Mott R (1997) EST_GENOME: a program to align spliced DNA sequences to unspliced genomic DNA. Comput Appl Biosci 13:477–478

    PubMed  CAS  Google Scholar 

  • Nagasaki H, Arita M, Nishizawa T, Suwa M, Gotoh O (2005) Species-specific variation of alternative splicing and transcriptional initiation in six eukaryotes. Gene 364:53–62

    Article  PubMed  CAS  Google Scholar 

  • Nagasaki H, Arita M, Nishizawa T, Suwa M, Gotoh O (2006) Automated classification of alternative splicing and transcriptional initiation and construction of visual database of classified patterns. Bioinformatics 22:1211–1216

    Article  PubMed  CAS  Google Scholar 

  • Nagy E, Maquat LE (1998) A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci 23:198–199

    Article  PubMed  CAS  Google Scholar 

  • Ner-Gaon H, Halachmi R, Savaldi-Goldstein S, Rubin E, Ophir R, Fluhr R (2004) Intron retention is a major phenomenon in alternative splicing in Arabidopsis. Plant J 39:877–885

    Article  PubMed  CAS  Google Scholar 

  • Novoyatleva T, Tang Y, Rafalska I, Stamm S (2006) Pre-mRNA missplicing as a cause of human disease. Prog Mol Subcell Biol 44:27–46

    Article  PubMed  CAS  Google Scholar 

  • Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, Yamanaka I, Kiyosawa H, Yagi K, Tomaru Y, Hasegawa Y, Nogami A, Schonbach C, Gojobori T, Baldarelli R, Hill DP, Bult C, Hume DA, Quackenbush J, Schriml LM, Kanapin A, Matsuda H, Batalov S, Beisel KW, Blake JA, Bradt D, Brusic V, Chothia C, Corbani LE, Cousins S, Dalla E, Dragani TA, Fletcher CF, Forrest A, Frazer KS, Gaasterland T, Gariboldi M, Gissi C, Godzik A, Gough J, Grimmond S, Gustincich S, Hirokawa N, Jackson IJ, Jarvis ED, Kanai A, Kawaji H, Kawasawa Y, Kedzierski RM, King BL, Konagaya A, Kurochkin IV, Lee Y, Lenhard B, Lyons PA, Maglott DR, Maltais L, Marchionni L, McKenzie L, Miki H, Nagashima T, Numata K, Okido T, Pavan WJ, Pertea G, Pesole G, Petrovsky N, Pillai R, Pontius JU, Qi D, Ramachandran S, Ravasi T, Reed JC, Reed DJ, Reid J, Ring BZ, Ringwald M, Sandelin A, Schneider C, Semple CA, Setou M, Shimada K, Sultana R, Takenaka Y, Taylor MS, Teasdale RD, Tomita M, Verardo R, Wagner L, Wahlestedt C, Wang Y, Watanabe Y, Wells C, Wilming LG, Wynshaw-Boris A, Yanagisawa M, et al (2002) Analysis of the mouse transcriptome based on functional annotation of 60, 770 full-length cDNAs. Nature 420:563–573

    Article  PubMed  Google Scholar 

  • Ouyang S, Zhu W, Hamilton J, Lin H, Campbell M, Childs K, Thibaud-Nissen F, Malek RL, Lee Y, Zheng L, Orvis J, Haas B, Wortman J, Buell CR (2007) The TIGR Rice Genome Annotation Resource: improvements and new features. Nucleic Acids Res 35:D883–887

    Article  PubMed  CAS  Google Scholar 

  • Reddy AS (2007) Alternative splicing of pre-messenger RNAs in plants in the genomic era. Annu Rev Plant Biol 58:267–294

    Article  PubMed  CAS  Google Scholar 

  • Sorek R, Shamir R, Ast G (2004) How prevalent is functional alternative splicing in the human genome? Trends Genet 20:68–71

    Article  PubMed  CAS  Google Scholar 

  • Stamm S, Ben-Ari S, Rafalska I, Tang Y, Zhang Z, Toiber D, Thanaraj TA, Soreq H (2005) Function of alternative splicing. Gene 344:1–20

    Article  PubMed  CAS  Google Scholar 

  • Stamm S, Riethoven JJ, Le Texier V, Gopalakrishnan C, Kumanduri V, Tang Y, Barbosa-Morais NL, Thanaraj TA (2006) ASD: a bioinformatics resource on alternative splicing. Nucleic Acids Res 34:D46–D55

    Article  PubMed  CAS  Google Scholar 

  • Stetefeld J, Ruegg MA (2005) Structural and functional diversity generated by alternative mRNA splicing. Trends Biochem Sci 30:515–521

    Article  PubMed  CAS  Google Scholar 

  • Sugnet CW, Kent WJ, Ares M Jr, Haussler D (2004) Transcriptome and genome conservation of alternative splicing events in humans and mice. Pac Symp Biocomput 2004:66–77

    Google Scholar 

  • Usuka J, Zhu W, Brendel V (2000) Optimal spliced alignment of homologous cDNA to a genomic DNA template. Bioinformatics 16:203–211

    Article  PubMed  CAS  Google Scholar 

  • Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, et al (2001) The sequence of the human genome. Science 291:1304–1351

    Article  PubMed  CAS  Google Scholar 

  • Wang BB, Brendel V (2006) Genomewide comparative analysis of alternative splicing in plants. Proc Natl Acad Sci USA 103:7175–7180

    Article  PubMed  CAS  Google Scholar 

  • Wortman JR, Haas BJ, Hannick LI, Smith RK Jr, Maiti R, Ronning CM, Chan AP, Yu C, Ayele M, Whitelaw CA, White OR, Town CD (2003) Annotation of the Arabidopsis genome. Plant Physiol 132:461–468

    Article  PubMed  CAS  Google Scholar 

  • Wu TD, Watanabe CK (2005) GMAP: a genomic mapping and alignment program for mRNA and EST sequences. Bioinformatics 21:1859–1875

    Article  PubMed  CAS  Google Scholar 

  • Xing Y, Resch A, Lee C (2004) The multiassembly problem: reconstructing multiple transcript isoforms from EST fragment mixtures. Genome Res 14:426–441

    Article  PubMed  CAS  Google Scholar 

  • Xing Y, Yu T, Wu YN, Roy M, Kim J, Lee C (2006) An expectation-maximization algorithm for probabilistic reconstructions of full-length isoforms from splice graphs. Nucleic Acids Res 34:3150–3160

    Article  PubMed  CAS  Google Scholar 

  • Yu J, Hu S, Wang J, Wong GK, Li S, Liu B, Deng Y, Dai L, Zhou Y, Zhang X, Cao M, Liu J, Sun J, Tang J, Chen Y, Huang X, Lin W, Ye C, Tong W, Cong L, Geng J, Han Y, Li L, Li W, Hu G, Huang X, Li W, Li J, Liu Z, Li L, Liu J, Qi Q, Liu J, Li L, Li T, Wang X, Lu H, Wu T, Zhu M, Ni P, Han H, Dong W, Ren X, Feng X, Cui P, Li X, Wang H, Xu X, Zhai W, Xu Z, Zhang J, He S, Zhang J, Xu J, Zhang K, Zheng X, Dong J, Zeng W, Tao L, Ye J, Tan J, Ren X, Chen X, He J, Liu D, Tian W, Tian C, Xia H, Bao Q, Li G, Gao H, Cao T, Wang J, Zhao W, Li P, Chen W, Wang X, Zhang Y, Hu J, Wang J, Liu S, Yang J, Zhang G, Xiong Y, Li Z, Mao L, Zhou C, Zhu Z, Chen R, Hao B, Zheng W, Chen S, Guo W, Li G, Liu S, Tao M, Wang J, Zhu L, Yuan L, Yang H (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. indica). Science 296:79–92

    Article  PubMed  CAS  Google Scholar 

  • Zavolan M, Kondo S, Schonbach C, Adachi J, Hume DA, Hayashizaki Y, Gaasterland T (2003) Impact of alternative initiation, splicing, and termination on the diversity of the mRNA transcripts encoded by the mouse transcriptome. Genome Res 13:1290–1300

    Article  PubMed  CAS  Google Scholar 

  • Zipursky SL, Wojtowicz WM, Hattori D (2006) Got diversity? Wiring the fly brain with Dscam. Trends Biochem Sci 31:581–588

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Broad Institute, 7 Cambridge Center, Cambridge, MA, 02142, USA

    B. J. Haas

Authors
  1. B. J. Haas
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Biology and Program in Molecular Plant Biology, Colorado State University, Fort Collins, CO, 80523, USA

    Anireddy S. N. Reddy

  2. Department of Microbiology, Thomas Jefferson University, Philadelphia, PA, 19107, USA

    Maxim Golovkin

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Haas, B.J. (2008). Analysis of Alternative Splicing in Plants with Bioinformatics Tools. In: Reddy, A.S.N., Golovkin, M. (eds) Nuclear pre-mRNA Processing in Plants. Current Topics in Microbiology and Immunology, vol 326. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76776-3_2

Download citation

Publish with us

Policies and ethics

Search

Navigation