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During the last decade, the cost of DNA sequencing technologies has decreased several orders of magnitude, with the proportional increase of speed and throughput. Human Genome Project took almost 15 years to complete the sequence of the human genome. With the second and third generation technologies, this can be done in the matter of days or hours. This progress and availability of sequencing instruments to virtually every researcher leads to replacing of many techniques with DNA sequencing and opens new venues of research. DNA sequencing is used to investigate basic biological phenomena, and is probably going to be increasingly used in the context of health care (preimplantation diagnostics, oncology, infectious diseases). Current trends are aiming towards the price of 1000$ for sequencing of one human genome. Without any doubt, we can expect improvement of existing and the development of fourth generation technologies in the coming years.

1. Manier J Caution: Replicating The Lifestyle Of DNA Guru Kary Mullis May Be Hazardous Journal/Chicago Tribune 1998;

2. Maxam AM, Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci USA 1977; 74: 560-4.

3. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977; 74: 5463-7.

4. Brownlee GG, Sanger F. Nucleotide sequences from the low molecular weight ribosomal RNA of Escherichia coli. J Mol Biol 1967; 23: 337-53.

5. Gilbert W, Maxam A. The nucleotide sequence of the lac operator. Proc Natl Acad Sci USA 1973; 70: 3581-4.

6. Sanger F, Donelson JE, Coulson AR, Kossel H, Fischer D. Use of DNA polymerase I primed by a synthetic oligonucleotide to determine a nucleotide sequence in phage fl DNA. Proc Natl Acad Sci USA 1973; 70: 1209-13.

7. Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, et al. Nucleotide sequence of bacteriophage phi X174 DNA. Nature 1977; 265: 687-95.

8. Sanger F, Coulson AR. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 1975; 94: 441-8.

9. Sanger F, Coulson AR, Friedmann T, Air GM, Barrell BG, Brown NL, et al. The nucleotide sequence of bacteriophage phiX174. J Mol Biol 1978; 125: 225-46.

10. Sanger F, Coulson AR. The use of thin acrylamide gels for DNA sequencing. FEBS Lett 1978; 87: 107-10.

11. Boulikas T, Hancock R. A highly sensitive technique for staining DNA and RNA in polyacrylamide gels using silver. J Biochem Biophys Methods 1981; 5: 219-28.

12. Somerville LL, Wang K. The ultrasensitive silver »protein« stain also detects nanograms of nucleic acids. Biochem Biophys Res Commun 1981; 102: 53-8.

13. Bassam BJ, Caetano-Anolles G, Gresshoff PM. Fast and sensitive silver staining of DNA in polyacrylamide gels. Anal Biochem 1991; 196: 80-3.

14. Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. Sequence and organization of the human mitochondrial genome. Nature 1981; 290: 457-65.

15. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 1995; 269: 496-512.

16. Goffeau A, Barrell BG, Bussey H, Davis RW, Dujon B, Feldmann H, et al. Life with 6000 genes. Science 1996; 274: 546, 563-47.

17. TCESC. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 1998; 282: 2012-8.

18. TAGI. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 2000; 408: 796-815.

19. Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, et al. The genome sequence of Drosophila melanogaster. Science 2000; 287: 2185-95.

20. Myers EW, Sutton GG, Delcher AL, Dew IM, Fasulo DP, Flanigan MJ, et al. A whole-genome assembly of Drosophila. Science 2000; 287: 2196-204.

21. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science 2001; 291: 1304-51.

22. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409: 860-921.

23. IHGS. Finishing the euchromatic sequence of the human genome. Nature 2004; 431: 931-45.

24. Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, et al. The diploid genome sequence of an individual human. PLoS Biol 2007; 5: e254.

25. Hood LE, Hunkapiller MW, Smith LM. Automated DNA sequencing and analysis of the human genome. Genomics 1987; 1: 201-12.

26. Prober JM, Trainor GL, Dam RJ, Hobbs FW, Robertson CW, Zagursky RJ, et al. A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides. Science 1987; 238: 336-41.

27. Swerdlow H, Gesteland R. Capillary gel electrophoresis for rapid, high resolution DNA sequencing. Nucleic Acids Res 1990; 18: 1415-9.

28. ABI. ABI PRISM 373 DNA sequencer with XL upgrade: User’s manual. 2001.

29. ABI. ABI Prism 310 Genetic analyzer: User’s manual. 2010.

30. ABI. ABI PRISM 377 DNA Sequencer For Sequencing and GeneScan Analysis Software Applications: User’s manual. 2000.

31. ABI, Hitachi. ABI PRISM 3100 Genetic Analyzer: User’s Manual. 2001.

32. ABI. Applied Biosystems 3730 and 3730xl DNA Ana - lyzers: Specification Sheet. 2006.

33. Kieleczawa J. Automated DNA scanners used in se - quencing laboratories. In: Kieleczawa J, editor. DNA Sequ encing: Optimizing the Process and Analysis, Volume 1. Sudbury: Jones and Bartlett Publishers, Inc., 2005: 123-30.

34. Men AE, Wilson P, Siemering K, Forrest S. Sanger DNA sequencing. In: Janitz M, editor. Next-Generation Sequen cing: Towards Personalized Medicine. Weinheim: Wiley-VCH Verlag GmbH, 2008: 3-11.

35. Drmanac R, Labat I, Brukner I, Crkvenjakov R. Sequen - cing of megabase plus DNA by hybridization: theory of the method. Genomics 1989; 4: 114-28.

36. Drmanac R, Strezoska Z, Labat I, Drmanac S, Crkve - njakov R. Reliable hybridization of oligonucleotides as short as six nucleotides. DNA Cell Biol 1990; 9: 527-34.

37. Drmanac R, Drmanac S, Chui G, Diaz R, Hou A, Jin H, et al. Sequencing by hybridization (SBH): advantages, achievements, and opportunities. Adv Biochem Eng Biotechnol 2002; 77: 75-101.

38. Strezoska Z, Paunesku T, Radosavljevic D, Labat I, Drma - nac R, Crkvenjakov R. DNA sequencing by hybridization: 100 bases read by a non-gel-based method. Proc Natl Acad Sci USA 1991; 88: 10089-93.

39. Drmanac R, Drmanac S, Strezoska Z, Paunesku T, Labat I, Zeremski M, et al. DNA sequence determination by hybridization: a strategy for efficient large-scale sequencing. Science 1993; 260: 1649-52.

40. Hacia JG. Resequencing and mutational analysis using oligonucleotide microarrays. Nat Genet 1999; 21: 42-7.

41. Pihlak A, Bauren G, Hersoug E, Lonnerberg P, Metsis A, Linnarsson S. Rapid genome sequencing with short universal tiling probes. Nat Biotechnol 2008; 26: 676-84.

42. Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 2010; 327: 78-81.

43. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature 2005; 437: 376-80.

44. Ronaghi M, Karamohamed S, Pettersson B, Uhlen M, Nyren P. Real-time DNA sequencing using detection of pyrophosphate release. Anal Biochem 1996; 242: 84-9.

45. Hyman ED. A new method of sequencing DNA. Anal Biochem 1988; 174: 423-36.

46. Ronaghi M, Uhlen M, Nyren P. A sequencing method based on real-time pyrophosphate. Science 1998; 281: 363-5.

47. Leamon JH, Lee WL, Tartaro KR, Lanza JR, Sarkis GJ, deWinter AD, et al. A massively parallel PicoTiterPlate based platform for discrete picoliter-scale polymerase chain reactions. Electrophoresis 2003; 24: 3769-77.

48. Nakano M, Komatsu J, Matsuura S, Takashima K, Kat - sura S, Mizuno A. Single-molecule PCR using water-in-oil emulsion. J Biotechnol 2003; 102: 117-24.

49. 454, Roche. GS FLX+ System. Flyer. 2011.

50. Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010; 11: 31-46.

51. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, et al. The complete genome of an individual by massively parallel DNA sequencing. Nature 2008; 452: 872-6.

52. Illumina. HiSeq sequencing systems: Specification sheet. 2011.

53. Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, et al. Accurate whole human genome sequencing using reversible terminator chemistry. Nature 2008; 456: 53-9.

54. Valouev A, Ichikawa J, Tonthat T, Stuart J, Ranade S, Peckham H, et al. A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res 2008; 18: 1051-63.

55. Eid J, Fehr A, Gray J, Luong K, Lyle J, Otto G, et al. Realtime DNA sequencing from single polymerase molecules. Science 2009; 323: 133-8.

56. Clarke J, Wu HC, Jayasinghe L, Patel A, Reid S, Bayley H. Continuous base identification for single-molecule nanopore DNA sequencing. Nat Nanotechnol 2009; 4: 265-70.

57. Branton D, Deamer DW, Marziali A, Bayley H, Benner SA, Butler T, et al. The potential and challenges of nanopore sequencing. Nat Biotechnol 2008; 26: 1146-1153.

58. Rothberg JM, Hinz W, Rearick TM, Schultz J, Mileski W, Davey M, et al. An integrated semiconductor device enabling non-optical genome sequencing. Nature 2011; 475: 348-52.

59. LifeTechnologies. Ion Proton: Specification sheet. 2012.

60. Ozsolak F, Platt AR, Jones DR, Reifenberger JG, Sass LE, McInerney P, et al. Direct RNA sequencing. Nature 2009; 461: 814-8.

61. Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, et al. Tumour evolution inferred by single-cell sequencing. Nature 2011; 472: 90-4.

62. Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, et al. mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods 2009; 6: 377-82.

63. Loman NJ, Misra RV, Dallman TJ, Constantinidou C, Gharbia SE, Wain J, et al. Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol 2012; 30: 434-9.

64. Lipson D, Raz T, Kieu A, Jones DR, Giladi E, Thayer E, et al. Quantification of the yeast transcriptome by singlemolecule sequencing. Nat Biotechnol 2009; 27: 652-8.

65. Marioni JC, Mason CE, Mane SM, Stephens M, Gilad Y. RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res 2008; 18: 1509-17.

66. Korshunova Y, Maloney RK, Lakey N, Citek RW, Bacher B, Budiman A, et al. Massively parallel bisulphite pyrosequencing reveals the molecular complexity of breast cancer- associated cytosine-methylation patterns obtained from tissue and serum DNA. Genome Res 2008; 18: 19-29.

67. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 2009; 461: 272-6.

68. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell 2007; 129: 823-37.

69. Pleasance ED, Cheetham RK, Stephens PJ, McBride DJ, Humphray SJ, Greenman CD, et al. A comprehensive catalogue of somatic mutations from a human cancer genome. Nature 2010; 463: 191-6.

70. Mertes F, Elsharawy A, Sauer S, van Helvoort JM, van der Zaag PJ, Franke A, et al. Targeted enrichment of genomic DNA regions for next-generation sequencing. Brief Funct Genomics 2011; 10: 374-86.

71. Marshall E. Human genome 10th anniversary. Waiting for the revolution. Science 2011; 331: 526-9.

72. Chiu RW, Chan KC, Gao Y, Lau VY, Zheng W, Leung TY, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma. Proc Natl Acad Sci USA 2008; 105: 20458-63.

73. Martin J, Cervero A, Mir P, Martinez-Conejero JA, Pellicer A, Simon C. The impact of next-generation sequencing technology on preimplantation genetic diagnosis and screening. Fertil Steril 2013; 99: 1054-1061 e1053.

74. Aparicio SA, Huntsman DG. Does massively parallel DNA resequencing signify the end of histopathology as we know it? J Pathol 2010; 220: 307-15.

75. Ezewudo M, Zwick ME. Evaluating rare variants in complex disorders using next-generation sequencing. Curr Psychiatry Rep 2013; 15: 349.

76. Kedes L, Campany G. The new date, new format, new goals and new sponsor of the Archon Genomics X PRIZE competition. Nat Genet 2011; 43: 1055-8.

77. Goldberg MD. Science at the crossroads: Fact or Fiction? J Med Biochem 2011; 30: 79-92.

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