Advertisement

Applications of Second Generation Sequencing Technologies in Complex Disorders

  • Mònica BayésEmail author
  • Simon Heath
  • Ivo Glynne Gut
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 12)

Abstract

Second generation sequencing (2ndGS) technologies generate unprecedented amounts of sequence data very rapidly and at relatively limited costs, allowing the sequence of a human genome to be completed in a few weeks. The principle is on the basis of generating millions of relatively short reads from amplified single DNA fragments using iterative cycles of nucleotide extensions. However, the data generated on this scale present new challenges in interpretation, data analysis and data management. 2ndGS technologies are becoming widespread and are profoundly impacting biomedical research. Common applications include whole-genome sequencing, target resequencing, characterization of structural and copy number variation, profiling epigenetic modifications, transcriptome sequencing and identification of infectious agents. New methodologies and instruments that will enable to sequence the complete human genome in less than a day at a cost of less than $1,000 are currently in development.

Keywords

Sequencing technologies Bioinformatics Personalized genomics 

References

  1. Ansorge WJ (2009) Next-generation DNA sequencing techniques. N Biotechnol 25(4):195–203PubMedCrossRefGoogle Scholar
  2. Bentley DR, Balasubramanian S, Swerdlow HP et al (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456:53–59PubMedCrossRefGoogle Scholar
  3. Brkanac Z, Spencer D, Shendure J et al (2009) IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23. Am J Hum Genet 84(5):692–697PubMedCrossRefGoogle Scholar
  4. Bryant DW Jr, Shen R, Priest HD, Wong WK, Mockler TC (2010) Supersplat–spliced RNA-seq alignment. Bioinformatics 26(12):1500–1505PubMedCrossRefGoogle Scholar
  5. Cirulli ET, Singh A, Shianna KV et al (2010) Screening the human exome: a comparison of whole genome and whole transcriptome sequencing. Genome Biol 11(5):R57PubMedGoogle Scholar
  6. Chen W, Kalscheuer V, Tzschach A et al (2008) Mapping translocation breakpoints by next-generation sequencing. Genome Res 18(7):1143–1149PubMedCrossRefGoogle Scholar
  7. Dames S, Durtschi J, Geiersbach K, Stephens J, Voelkerding KV (2010) Comparison of the Illumina genome analyzer and roche 454 GS FLX for resequencing of hypertrophic cardiomyopathy-associated genes. J Biomol Tech 21(2):73–80PubMedGoogle Scholar
  8. Diehl F, Li M, He Y, Kinzler KW, Vogelstein B, Dressman D (2006) BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods 3(7):551–559PubMedCrossRefGoogle Scholar
  9. Ding L, Ellis MJ, Li S, Larson DE et al (2010) Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464(7291):999–1005PubMedCrossRefGoogle Scholar
  10. Feng H, Shuda M, Chang Y, Moore PS (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319(5866):1096–1100PubMedCrossRefGoogle Scholar
  11. Hoffmann C, Minkah N, Leipzig J et al (2007) DNA bar coding and pyrosequencing to identify rare HIV drug resistance mutations. Nucleic Acids Res 35(13):e91PubMedCrossRefGoogle Scholar
  12. Holt RA, Jones SJ (2008) The new paradigm of flow cell sequencing. Genome Res 18(6):839–846PubMedCrossRefGoogle Scholar
  13. Jones S, Hruban RH, Kamiyama M et al (2009) Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324(5924):217PubMedCrossRefGoogle Scholar
  14. Koboldt DC, Chen K, Wylie T et al (2009) VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics 25(17):2283–2285PubMedCrossRefGoogle Scholar
  15. Koboldt DC, Ding L, Mardis ER, Wilson RK (2010) Challenges of sequencing human genomes. Brief Bioinform 11(5):484–498PubMedCrossRefGoogle Scholar
  16. Korlach J, Bjornson KP, Chaudhuri BP et al (2010) Real-time DNA sequencing from single polymerase molecules. Methods Enzymol 472:431–455PubMedCrossRefGoogle Scholar
  17. Ku CS, Loy EY, Salim A, Pawitan Y, Chia KS (2010) The discovery of human genetic variations and their use as disease markers: past, present and future. J Hum Genet 55(7):403–415PubMedCrossRefGoogle Scholar
  18. Li H, Handsaker B, Wysoker A et al (2009) The sequence alignment/map format and SAMtools. Bioinformatics 25(16):2078–2079PubMedCrossRefGoogle Scholar
  19. Li H, Homer N (2010) A survey of sequence alignment algorithms for next-generation sequencing. Brief Bioinform 11(5):473–483PubMedCrossRefGoogle Scholar
  20. Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409(6822):860–921PubMedCrossRefGoogle Scholar
  21. Lister R, Ecker JR (2009) Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res 19(6):959–966PubMedCrossRefGoogle Scholar
  22. Lister R, Pelizzola M, Dowen RH et al (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315–322PubMedCrossRefGoogle Scholar
  23. Lupski JR, Reid JG, Gonzaga-Jauregui C et al (2010) Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med 362(13):1181–1191PubMedCrossRefGoogle Scholar
  24. MacLean D, Jones JD, Studholme DJ (2009) Application of ‘next-generation’ sequencing technologies to microbial genetics. Nat Rev Microbiol 7(4):287–296PubMedGoogle Scholar
  25. Maher CA, Palanisamy N, Brenner JC et al (2009) Chimeric transcript discovery by paired-end transcriptome sequencing. Proc Natl Acad Sci U S A 106(30):12353–12358PubMedCrossRefGoogle Scholar
  26. Mamanova L, Coffey AJ, Scott CE et al (2010) Target-enrichment strategies for next-generation sequencing. Nat Methods 7(2):111–118PubMedCrossRefGoogle Scholar
  27. Mardis ER (2009) New strategies and emerging technologies for massively parallel sequencing: applications in medical research. Genome Med 1(4):40PubMedCrossRefGoogle Scholar
  28. Margulies M, Egholm M, Altman WE et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380PubMedGoogle Scholar
  29. Maxam AM, Gilbert W (1977) A new method for sequencing DNA. Proc Natl Acad Sci 74(2):560–564PubMedCrossRefGoogle Scholar
  30. Medvedev P, Stanciu M, Brudno M (2009) Computational methods for discovering structural variation with next-generation sequencing. Nat Methods 6(11 Suppl):S13–S20PubMedCrossRefGoogle Scholar
  31. McCarthy MI (2009) Exploring the unknown: assumptions about allelic architecture and strategies for susceptibility variant discovery. Genome Med 1(7):66PubMedCrossRefGoogle Scholar
  32. Morgan JE, Carr IM, Sheridan E et al (2010) Genetic diagnosis of familial breast cancer using clonal sequencing. Hum Mutat 31(4):484–491PubMedCrossRefGoogle Scholar
  33. Morozova O, Hirst M, Marra MA (2009) Applications of new sequencing technologies for transcriptome analysis. Annu Rev Genomics Hum Genet 10:135–151PubMedCrossRefGoogle Scholar
  34. Ng SB, Buckingham KJ, Lee C et al (2010) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42(1):30–35PubMedCrossRefGoogle Scholar
  35. Nikopoulos K, Gilissen C, Hoischen A et al (2010) Next-generation sequencing of a 40 Mb linkage interval reveals TSPAN12 mutations in patients with familial exudative vitreoretinopathy. Am J Hum Genet 86(2):240–247PubMedCrossRefGoogle Scholar
  36. Nygaard S, Jacobsen A, Lindow M et al (2009) Identification and analysis of miRNAs in human breast cancer and teratoma samples using deep sequencing. BMC Med Genomics 2:35PubMedGoogle Scholar
  37. Palacios G, Druce J, Du L et al (2008) A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med 358(10):991–998PubMedCrossRefGoogle Scholar
  38. Park PJ (2008) Epigenetics meets next-generation sequencing. Epigenetics 3(6):318–321PubMedCrossRefGoogle Scholar
  39. Robison K (2010) Application of second-generation sequencing to cancer genomics. Brief Bioinform 11:524–534 (Epub ahead of print)Google Scholar
  40. Ronaghi M, Karamohamed S, Pettersson B et al (1996) Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem 242:84–89PubMedCrossRefGoogle Scholar
  41. Sanger F, Nicklen S, Coulson AR (1977) DNA Sequencing with chain-terminating inhibitors. Proc Natl Acad Sci 74:546–567CrossRefGoogle Scholar
  42. Schadt EE, Turner S, Kasarskis A (2010) A window into third-generation sequencing. Hum Mol Genet 19(R2):R227–R240PubMedCrossRefGoogle Scholar
  43. Shah SP, Köbel M, Senz J et al (2009) Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 360(26):2719–2729PubMedCrossRefGoogle Scholar
  44. Sobreira NL, Cirulli ET, Avramopoulos D et al (2010) Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. PLoS Genet 6(6):e1000991PubMedCrossRefGoogle Scholar
  45. Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458(7239):719–724PubMedCrossRefGoogle Scholar
  46. Tang F, Barbacioru C, Nordman E et al (2010) RNA-Seq analysis to capture the transcriptome landscape of a single cell. Nat Protoc 5(3):516–535PubMedCrossRefGoogle Scholar
  47. The international cancer genome consortium. Hudson TJ, Anderson W, Artez A et al (2010) International network of cancer genome projects. Nature 464(7291):993–998CrossRefGoogle Scholar
  48. Trapnell C, Pachter L, Salzberg SL (2009) Tophat: discovering splice junctions with RNA-Seq. Bioinformatics 25(9):1105–1111PubMedCrossRefGoogle Scholar
  49. Uziel T, Karginov FV, Xie S et al (2009) The MIR-17~92 cluster collaborates with the Sonic Hedgehog pathway in medulloblastoma. Proc Natl Acad Sci U S A 106(8):2812–2817PubMedCrossRefGoogle Scholar
  50. Vasta V, Ng SB, Turner EH, Shendure J, Hahn SH (2009) Next generation sequence analysis for mitochondrial disorders. Genome Med 1(10):100PubMedCrossRefGoogle Scholar
  51. Venter JC, Adams MD, Myers EW et al (2001) The sequence of the human genome. Science 291(5507):1304–1351PubMedCrossRefGoogle Scholar
  52. Voelkerding KV, Dames SA, Durtschi JD (2009) Next-generation sequencing: from basic research to diagnostics. Clin Chem 55(4):641–658PubMedCrossRefGoogle Scholar
  53. Volpi L, Roversi G, Colombo EA et al (2010) Targeted next-generation sequencing appoints c16orf57 as clericuzio-type poikiloderma with neutropenia gene. Am J Hum Genet 86(1):72–76PubMedCrossRefGoogle Scholar
  54. Walsh T, Lee MK, Casadei S et al (2010) Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci 107(28):12629–12633PubMedCrossRefGoogle Scholar
  55. Weise A, Timmermann B, Grabherr M et al (2010) High-throughput sequencing of microdissected chromosomal regions. Eur J Hum Genet 18(4):457–462PubMedCrossRefGoogle Scholar
  56. Wyman SK, Parkin RK, Mitchell PS et al (2009) Repertoire of microRNAs in epithelial ovarian cancer as determined by next generation sequencing of small RNA cDNA libraries. PLoS One 4(4):e5311PubMedCrossRefGoogle Scholar
  57. Yeager M, Xiao N, Hayes RB et al (2008) Comprehensive resequence analysis of a 136 kb region of human chromosome 8q24 associated with prostate and colon cancers. Hum Genet 124(2):161–170PubMedCrossRefGoogle Scholar
  58. Zhao Q, Caballero OL, Levy S et al (2009) Transcriptome-guided characterization of genomic rearrangements in a breast cancer cell line. Proc Natl Acad Sci U S A 106(6):1886–1891PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Centro Nacional de Análisis GenómicoBarcelonaSpain

Personalised recommendations