SpringerLink
Log in

Genome Sequencing and Genomic Technologies in Drug Discovery and Development

  • Chapter
Handbook of Industrial Cell Culture

  • 578 Accesses

Abstract

Drug discovery and development is rooted in empiricism, exemplified by testing of compounds in animal models of disease, and on the identification and optimization of the active ingredients in traditional folk medicines. Over the past century, this has radically changed with the introduction of new scientific paradigms and cutting-edge technologies into the pharmaceutical R&D process (1,2) (Fig. 1). These innovations include the automation of compound screening (3) and improvements in medicinal chemistry, along with the development of combinatorial chemistry (4), and advances in molecular biology. Most of these technologies have focused on increased throughput through one portion of the drug discovery and development pipeline and the result has been to relocate—rather than eliminate—the bottlenecks and failures in the overall process. The attrition rate of the drug discovery and development pipeline continues to be a major problem, as highlighted by the large number of compounds that fail in clinical trials because of poor pharmacology, toxicity, and/or lack of efficacy (5,6). At the same time, economic factors apply, increasing pressure to reduce this attrition (7).

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Drews, J. (1999) In Quest of Tomorrows Medicines. Springer, New York, NY, p. 272.

    Book  Google Scholar 

  2. Drews, J. (2000) Drug discovery, a historical perspective. Science 287, 1960–1964.

    Article  CAS  Google Scholar 

  3. Broach, J. R. and Thorner, J. (1996) High-throughput screening for drug discovery. Nature 384(suppl), 14–16.

    Article  CAS  Google Scholar 

  4. Hogan, J. C., Jr. (1996) Directed combinatorial chemistry. Nature 384(suppl), 17–19.

    CAS  Google Scholar 

  5. Tapolczay, D., Chorlton, A., and McCubbin, Q. (2000), Probing drug structure improves the odds. Drug Discovery and Development 2000, 30–33.

    Google Scholar 

  6. Prentis, R. A., Lis, Y., and Walker, S. R. (1988) Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964–1985). Br. J. Clin. Pharmacol. 25, 387–396.

    Article  CAS  Google Scholar 

  7. Drews, J. and Ryser, S. (1997) The role of innovation in drug development. Nat. Biotechnol. 15, 1318–1319.

    Article  CAS  Google Scholar 

  8. Aebersold, R., Hood, L. E., and Watts, J. D. (2000) Equip** scientists for the new biology. Nat. Biotechnol. 18, 359.

    Article  CAS  Google Scholar 

  9. Brent, R. (2000) Genomic biology. Cell 100, 169–183.

    Article  CAS  Google Scholar 

  10. Vidal, M. (2001) A biological atlas of functional maps. Cell 104, 333–339.

    Article  CAS  Google Scholar 

  11. Hartwell, L. H., et al. (1999) From molecular to modular cell biology. Nature 402(suppl), C47–52.

    Article  CAS  Google Scholar 

  12. Evans, G. A. (2000) Designer science and the “omic” revolution. Nat. Biotechnol. 18, 127.

    Article  CAS  Google Scholar 

  13. Cockett, M., Dracopoli, N., and Sigal, E. (2000) Applied genomics, integration of the technology within pharmaceutical research and development. Curr. Opin. Biotechnol. 11, 602–609.

    Article  CAS  Google Scholar 

  14. Gelbert, L. M. and Gregg, R. E. (1997) Will genetics really revolutionize the drug discovery process? Curr. Opin. Biotechnol. 8, 669–674.

    Article  CAS  Google Scholar 

  15. Bumol, T. F. and Watanabe, A. M. (2001) Genetic information, genomic technologies, and the future of drug discovery. JAMA 285, 551–555.

    Article  CAS  Google Scholar 

  16. Lewin, B., (2000) Genes VII. Oxford University Press, Oxford, NY, p. 990.

    Google Scholar 

  17. Perera, F. (1997) Environment and cancer, who are susceptible? Science 278, 1068–1073.

    Article  CAS  Google Scholar 

  18. Fearon, E. R. (1997) Human cancer syndromes, clues to the origin and nature of cancer. Science 278, 1043–1050.

    Article  CAS  Google Scholar 

  19. Collins, F. S. (1995) Positional cloning moves from perditional to traditional. Nat. Genet. 9, 347–350.

    Article  CAS  Google Scholar 

  20. Cohen, J. (1997) The genomics gamble. Science 275, 767–772.

    Article  CAS  Google Scholar 

  21. Schafer, A. J. and Hawkins, J. R. (1998) DNA variation and the future of human genetics. Nat. Biotechnol. 16, 33–39.

    Article  CAS  Google Scholar 

  22. Lander, E. S. (1996) The new genomics, global views of biology. Science 274, 536–539.

    Article  CAS  Google Scholar 

  23. Gewolb, J. (2001) Genome research. DNA sequencers to go bananas? Science 293, 585–586.

    Article  CAS  Google Scholar 

  24. O’Brien, S. J., Eizirik, E., and Murphy, W. J. (2001), GENOMICS: On choosing mammalian genomes for sequencing. Science 292, 2264–2266.

    Article  Google Scholar 

  25. Strohman, R. C. (1997) The coming Kuhnian revolution in biology. Nat. Biotechnol. 15, 194–200.

    Article  CAS  Google Scholar 

  26. Drews, J. (2000) Drug discovery today-and tomorrow. Drug Discov Today 5, 2–4.

    Article  Google Scholar 

  27. Drews, J. (1997) Strategic choices facing the pharmaceutical industry, a case for innovation. Drug Discov. Today, 72–78.

    Google Scholar 

  28. Bork, and Copley, R. (2001) Genome speak. Nature 409, 815.

    Article  Google Scholar 

  29. Morell, V. (1996) Life’s last domain. Science 273, 1043–1045.

    Article  CAS  Google Scholar 

  30. Bult, C. J., et al. (1996) Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science 273, 1058–1073.

    CAS  Google Scholar 

  31. NCBI, National Center for Biotechnology Information. (http://www.NCBI.NLM.NIH.gov)

    Google Scholar 

  32. Dacks, J. B. and Doolittle, W. F. (2001) Reconstructing/Deconstructing the earliest eukaryotes. How comparative genomics can help. Cell 107, 419–425.

    Article  CAS  Google Scholar 

  33. Mushegian, A. R., et al. (1997) Positionally cloned human disease genes, patterns of evolutionary conservation and functional motifs. Proc. Natl. Acad. Sci. USA 94, 5831–5836.

    Article  CAS  Google Scholar 

  34. Rosamond, J. and Allsop, A. (2000) Harnessing the power of the genome in the search for new antibiotics. Science 287, 1973–1976.

    Article  CAS  Google Scholar 

  35. Broder, S. and Venter, J. C. (2000) Sequencing the entire genomes of free-living organisms, the foundation of pharmacology in the new millennium. Annu. Rev. Pharmacol. Toxicol 40, 97–132.

    Article  CAS  Google Scholar 

  36. Koonin, E. V. (1997) Big time for small genomes. Genome Res 7, 418–421.

    CAS  Google Scholar 

  37. Davuluri, R. V., Grosse, I., and Zhang, M. Q. (2001) Computational identification of promoters and first exons in the human genome. Nat. Genet. 29, 412–417.

    Article  CAS  Google Scholar 

  38. Pilpel, Y., Sudarsanam, and Church, G. M. (2001) Identifying regulatory networks by combinatorial analysis of promoter elements. Nat. Genet. 29, 153–159.

    Article  CAS  Google Scholar 

  39. Drysdale, C. M., et al. (2000) Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc. Natl. Acad. Sci. USA 97, 10,483–10,488.

    Article  CAS  Google Scholar 

  40. Winzeler, E. A., et al. (1999) Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science 285, 901–906.

    Article  CAS  Google Scholar 

  41. Shoemaker, D. D., et al. (1996) Quantitative phenotypic analysis of yeast deletion mutants using a highly parallel molecular bar-coding strategy. Nat. Genet. 14, 450–456.

    Article  CAS  Google Scholar 

  42. Hughes, T. R., et al. (2000) Functional discovery via a compendium of expression profiles. Cell 102, 109–126.

    Article  CAS  Google Scholar 

  43. Scangos, G. (1997) Drug discovery in the postgenomic era. Nat. Biotechnol. 15, 1220–1221.

    Article  CAS  Google Scholar 

  44. Matthews, D. J. and Kopczynski, J. (2001), Using model-system genetics for drugbased target discovery. Drug Discov. Today 6, 141–149.

    Article  CAS  Google Scholar 

  45. Baltimore, D. (2001) Our genome unveiled. Nature 409, 814–816.

    Article  CAS  Google Scholar 

  46. Pennisi, E. (2001) The human genome. Science 291, 1177–1180.

    Article  CAS  Google Scholar 

  47. Collins, F. and Galas, D. (1993) A new five-year plan for the U.S. Human Genome Project. Science 262, 43–46.

    Article  CAS  Google Scholar 

  48. Roberts, L. (2001) The human genome. Controversial from the start. Science 291, 1182–1188.

    Article  CAS  Google Scholar 

  49. Collins, F. S., et al. (1998) New Goals for the U.S. Human Genome Project, 1998–2003. Science 282, 682–689.

    Article  CAS  Google Scholar 

  50. Lander, E. S., et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921.

    Article  CAS  Google Scholar 

  51. Venter, J. C., et al. (2001) The sequence of the human genome. Science 291, 1304–1351.

    Article  CAS  Google Scholar 

  52. Aach, J., et al. (2001) Computational comparison of two draft sequences of the human genome. Nature 409, 856–859.

    Article  CAS  Google Scholar 

  53. Wright, F. A., et al. (2001) A draft annotation and overview of the human genome. Genome Biol. 2, 25.

    Google Scholar 

  54. Claverie, J.M. (2001) Gene number. What if there are only 30,000 human genes? Science 291, 1255–1257.

    Article  CAS  Google Scholar 

  55. Green, E. D. and Chakravarti, A. (2001) The human genome sequence expedition, views from the “base camp.” Genome Res. 11, 645–651.

    Article  CAS  Google Scholar 

  56. Cheung, V. G., et al. (2001) Integration of cytogenetic landmarks into the draft sequence of the human genome. Nature 409, 953–958.

    Article  CAS  Google Scholar 

  57. Futreal, A., et al. (2001) Cancer and genomics. Nature 409, 850–852.

    Article  CAS  Google Scholar 

  58. Fahrer, A. M., et al. (2001) A genomic view of immunology. Nature 409, 836–838.

    Article  CAS  Google Scholar 

  59. Nestler, E. J. and Landsman, D. (2001) Learning about addiction from the genome. Nature 409, 834–835.

    Article  CAS  Google Scholar 

  60. Clayton, J. D., Kyriacou, C., and Reppert, S. M. (2001) Kee** time with the human genome. Nature 409, 829–831.

    Article  CAS  Google Scholar 

  61. Li, W. H., et al. (2001) Evolutionary analyses of the human genome. Nature 409, 847–849.

    Article  CAS  Google Scholar 

  62. Caron, H., et al. (2001) The human transcriptome map, clustering of highly expressed genes in chromosomal domains. Science 291, 1289–1292.

    Article  CAS  Google Scholar 

  63. Peltonen, L. and McKusick, V. A. (2001) Genomics and medicine, dissecting human disease in the postgenomic era. Science 291, 1224–1229.

    Article  CAS  Google Scholar 

  64. Collins, F. S. and McKusick, V. A. (2001) Implications of the Human Genome Project for medical science. JAMA 285, 540–544.

    Article  CAS  Google Scholar 

  65. McKusick, V. A. (2001) The anatomy of the human genome, a neo-Vesalian basis for medicine in the 21st century. JAMA 286, 2289–2295.

    Article  CAS  Google Scholar 

  66. Sander, C. (2000) Genomic medicine and the future of health care. Science 287, 1977–1978.

    Article  CAS  Google Scholar 

  67. Walsh, S. and Barrell, B. (1996) The Saccharomyces cerevisiae genome on the World Wide Web. Trends Genet 12, 276–277.

    Article  CAS  Google Scholar 

  68. Hieter, Bassett D. E., and Valle, D. (1996) The yeast genome—a common currency. Nat. Genet. 13, 253–255.

    Article  CAS  Google Scholar 

  69. Botstein, D., Chervitz, S. A., and Cherry, J. M. (1997) Yeast as a model organism. Science 277, 1259–1260.

    Article  CAS  Google Scholar 

  70. Mewes, H. W., et al. (1997) Overview of the yeast genome. Nature 387(suppl), 7–65.

    Article  Google Scholar 

  71. Kumar, A., et al. (2002) An integrated approach for finding overlooked genes in yeast. Nat. Biotechnol 20, 58–63.

    Article  CAS  Google Scholar 

  72. Oliver, S. (2002) ‘To-day, we have naming of parts.’ Nat. Biotechnol. 20, 27–28.

    Article  CAS  Google Scholar 

  73. Pennisi, E. (1998) Worming secrets from the C. elegans genome. Science 282, 1972–1974.

    Article  CAS  Google Scholar 

  74. The Caenorhabditis elegans Sequencing Consortium, Genome Sequence of the Nematode C. elegans, a platform for investigating biology. Science 282, 2012–2018.

    Google Scholar 

  75. Bargmann, C. I. (1998) Neurobiology of the Caenorhabditis elegans genome. Science 282, 2028–2033.

    Article  CAS  Google Scholar 

  76. Ruvkun, G. and Hobert, O. (1998) The taxonomy of developmental control in Caenorhabditis elegans. Science 282, 2033–2041.

    Article  CAS  Google Scholar 

  77. Adams, M. D., et al. (2000) The genome sequence of Drosophila melanogaster. Science 287, 2185–2195.

    Article  Google Scholar 

  78. Kornberg, T. B. and Krasnow, M. A. (2000) The Drosophila genome sequence, implications for biology and medicine. Science 287, 2218–2220.

    Article  CAS  Google Scholar 

  79. Pennisi, E. (2000) Ideas fly at gene-finding jamboree. Science 287, 2182–2184.

    Article  CAS  Google Scholar 

  80. Myers, E. W., et al. (2000) A whole-genome assembly of Drosophila. Science 287, 2196–2204.

    Article  CAS  Google Scholar 

  81. Rubin, G. M., et al. (2000) Comparative genomics of the eukaryotes. Science 287, 2204–2215.

    Article  CAS  Google Scholar 

  82. Doolittle, R. F. (1997) A bug with excess gastric avidity. Nature 388, 515–516.

    Article  CAS  Google Scholar 

  83. Tomb, J. F., et al., The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388, 539–547.

    Google Scholar 

  84. Covacci, A., et al. (1999) Helicobacter pylori virulence and genetic geography. Science 284, 1328–1333.

    Article  CAS  Google Scholar 

  85. Alm, R. A., et al. (1999) Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397, 176–180.

    Google Scholar 

  86. Bjorkholm, B., et al. (2001) Comparison of genetic divergence and fitness between two subclones of Helicobacter pylori. Infect. Immun. 69, 7832–7838.

    Article  CAS  Google Scholar 

  87. Bjorkholm, B. M., et al. (2001) Genomics and proteomics converge on Helicobacter pylori. Curr. Opin. Microbiol. 4, 237–245.

    Article  CAS  Google Scholar 

  88. Detweiler, C. S., Cunanan, D. B., and Falkow, S. (2001) Host microarray analysis reveals a role for the Salmonella response regulator phoP in human macrophage cell death. Proc. Natl. Acad. Sci. USA 98, 5850–5855.

    Article  CAS  Google Scholar 

  89. Young, D. B. (1998) Blueprint for the white plague. Nature 393, 515–516.

    Article  CAS  Google Scholar 

  90. Cole, S. T., et al. (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544.

    Article  CAS  Google Scholar 

  91. Cole, S. T., et al. (2001) Massive gene decay in the leprosy Bacillus. Nature 409, 1007–1011.

    Article  CAS  Google Scholar 

  92. Wahlgren, M. and Bejarano, M. T. (1999) A blueprint of ‘bad air’. Nature 400, 506–507.

    Article  CAS  Google Scholar 

  93. Bowman, S., et al. (1999) The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature 400, 532–538.

    Article  CAS  Google Scholar 

  94. Gardner, M. J., et al. (1998) Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 282, 1126–1132.

    Article  CAS  Google Scholar 

  95. Blattner, F. R., et al. (1997) The complete genome sequence of Escherichia coli K-12. Science 277, 1453–1474.

    Article  CAS  Google Scholar 

  96. Pennisi, E., Laboratory workhorse decoded. Science 277, 1432–1434.

    Google Scholar 

  97. Pennisi, E. (2001) Microbial genomes, new genome a boost to plant studies. Science 294, 2266a.

    Article  Google Scholar 

  98. Wood, D. W., et al. (2001) The genome of the natural genetic engineer Agrobacterium tumefaciens C58. Science 294, 2317–2323.

    Article  CAS  Google Scholar 

  99. Goodner, B., et al. (2001) Genome sequence of the plant pathogen and biotechnology agent Agrobacterium tumefaciens C58. Science 294, 2323–2328.

    Article  CAS  Google Scholar 

  100. Galas, D. J. (2001) Sequence interpretation, making sense of the sequence. Science 291, 1257–1260.

    Article  CAS  Google Scholar 

  101. Pennisi, E. (2001) What’s next for the genome centers? Science 291, 1204–1207.

    Article  CAS  Google Scholar 

  102. Fishman, M. C. (2001) Genomics. Zebrafish-the canonical vertebrate. Science 294, 1290–1291.

    Article  CAS  Google Scholar 

  103. Vogel, G. (2000) Genetics, Zebrafish earns its stripes in genetic screens. Science 288, 1160–1161.

    Article  CAS  Google Scholar 

  104. Patton, E. E. and Zon, L. I. (2001) The art and design of genetic screens, zebrafish. Nat. Rev. Genet. 2, 956–966.

    Article  CAS  Google Scholar 

  105. Roush, W. (1997) Developmental biology, a Zebrafish genome project? Science 275, 923.

    Article  CAS  Google Scholar 

  106. Duyk, G. and Schmitt, K. (2001) Fish x 3. Nat. Genet. 27, 8–9.

    Article  CAS  Google Scholar 

  107. Nadeau, J. H., et al. (2001) Sequence interpretation, functional annotation of mouse genome sequences. Science 291, 1251–1255.

    Article  CAS  Google Scholar 

  108. Rulicke, T. (1996) Transgenic technology, an introduction. Int. J. Exp. Pathol. 77, 243–245.

    CAS  Google Scholar 

  109. Dayan, A. D. (1996) Transgenic rodents in toxicology. Int. J. Exp. Pathol. 77, 251–256.

    CAS  Google Scholar 

  110. Gewolb, J. (2001) Genomics, animals line up to be sequenced. Science 293, 409–410.

    Article  CAS  Google Scholar 

  111. The Arabidopsis Genome Initiative, Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796–815.

    Google Scholar 

  112. Maloof, J. N., et al. (2001) Natural variation in light sensitivity of Arabidopsis. Nat. Genet. 29, 441–446.

    Article  CAS  Google Scholar 

  113. Millar, A. J. (2001) Light responses of a plastic plant. Nat. Genet. 29, 357–358.

    Article  CAS  Google Scholar 

  114. Quigley, R. A., Rosenberg, J. M., Shachar-Hill, Y., Bohnert, H. J. (2001) From genome to function, the Arabidopsis aquaporins. Genome Biology http://www.genomebiology.com/2001/3/1/research/0001.1.

    Google Scholar 

  115. Botstein, D., et al. (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32, 314–331.

    CAS  Google Scholar 

  116. Risch, N. and Merikangas, K. (1996) The future of genetic studies of complex human diseases. Science 273, 1516–1517.

    Article  CAS  Google Scholar 

  117. Nebert, D. W. (1997) Polymorphisms in drug-metabolizing enzymes, what is their clinical relevance and why do they exist? Am. J. Hum. Genet. 60, 265–271.

    CAS  Google Scholar 

  118. Puga, A., et al. (1997) Genetic polymorphisms in human drug-metabolizing enzymes, potential uses of reverse genetics to identify genes of toxicological relevance. Crit. Rev. Toxicol. 27, 199–222.

    Article  CAS  Google Scholar 

  119. Sachse, C., et al. (1997) Cytochrome P450 2D6 variants in a caucasian population, allele frequencies and phenotypic consequences. Am. J. Hum. Genet. 60, 284–295.

    CAS  Google Scholar 

  120. Meyer, U. A. and Zanger, U. M. (1997) Molecular mechanisms of genetic polymorphisms of drug metabolism. Annu. Rev. Pharmacol. Toxicol. 37, 269–296.

    Article  CAS  Google Scholar 

  121. Nakajima, T., et al. (1995) Expression and polymorphism of glutathione S-transferase in human lungs, risk factors in smoking-related lung cancer. Carcinogenesis 16, 707–711.

    Article  CAS  Google Scholar 

  122. Yengi, L., et al. (1996) Polymorphism at the glutathione S-transferase locus GSTM3, interactions with cytochrome P450 and glutathione S-transferase genotypes as risk factors for multiple cutaneous basal cell carcinoma. Cancer Res. 56, 1974–1977.

    CAS  Google Scholar 

  123. Norton, R. M. (2001) Clinical pharmacogenomics, applications in pharmaceutical R&D. Drug Discov. Today 6, 180–185.

    Article  Google Scholar 

  124. Roses, A. D. (2001) How will pharmacogenetics impact the future of research and development? Drug Discov. Today 6, 59–60.

    Article  Google Scholar 

  125. Nickerson, D. A., et al., Identification of clusters of biallelic polymorphic sequence-tagged sites (pSTSs) that generate highly informative and automatable markers for genetic linkage map**. Genomics 12, 377–387.

    Google Scholar 

  126. Wang, D. G., et al., Large-scale identification, map**, and genoty** of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082.

    Google Scholar 

  127. Chakravarti, A. It’s raining SNPs, hallelujah? Nat. Genet. 19, 216–217.

    Google Scholar 

  128. Clark, A. G., et al., Haplotype structure and population genetic inferences from nucleotidesequence variation in human lipoprotein lipase. Am. J. Hum. Genet. 63, 595–612.

    Google Scholar 

  129. Nickerson, D. A., et al., DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat. Genet. 19, 233–240.

    Google Scholar 

  130. Sachidanandam, R., et al., A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature 409, 928–933.

    Google Scholar 

  131. **ao, W. and Oefner, J., Denaturing high-performance liquid chromatography, a review. Hum. Mutat. 17, 439–474.

    Google Scholar 

  132. Johnson, G. C., et al., Haplotype tagging for the identification of common disease genes. Nat. Genet. 29, 233–237.

    Google Scholar 

  133. Shi, M. M., Bleavins, M. R., and de la Iglesia, F. A. (1999) Technologies for detecting genetic polymorphisms in pharmacogenomics. Mol. Diagn. 4, 343–351.

    Article  CAS  Google Scholar 

  134. Tillib, S. V. and Mirzabekov, A. D. (2001) Advances in the analysis of DNA sequence variations using oligonucleotide microchip technology. Curr. Opin. Biotechnol. 12, 53–58.

    Article  CAS  Google Scholar 

  135. Patil, N., et al., Blocks of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21. Science 294, 1719–1723.

    Google Scholar 

  136. Kwok, Y. (2001) GENOMICS, Genetic association by whole-genome analysis? Science 294, 1669–1670.

    Article  CAS  Google Scholar 

  137. Helmuth, L. (2001) Genome research, map of the human genome 3.0. Science 293, 583–585.

    Article  CAS  Google Scholar 

  138. Lander, E. S. (1999) Array of hope. Nat. Genet. 21(suppl), 3–4.

    Article  CAS  Google Scholar 

  139. Thomas, S. (1980) Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc. Natl. Acad. Sci. USA 77, 5201–5205.

    Article  CAS  Google Scholar 

  140. Roberts, L. (1991) Gambling on a shortcut to genome sequencing. Science 252, 1618,1619.

    Article  CAS  Google Scholar 

  141. Bonaldo, M. F., Lennon, G., and Soares, M. B. (1996) Normalization and subtraction, two approaches to facilitate gene discovery. Genome Res. 6, 791–806.

    Article  CAS  Google Scholar 

  142. Liang, P. and Pardee, A. B. (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257, 967–971.

    Article  CAS  Google Scholar 

  143. Liang, P., et al. (1995) Analysis of altered gene expression by differential display. Methods Enzymol. 254, 304–321.

    Article  CAS  Google Scholar 

  144. Liang, P. and A. B. Pardee (1998) Differential display. A general protocol. Mol. Biotechnol. 10, 261–267.

    Article  CAS  Google Scholar 

  145. Velculescu, V. E., et al. (1995) Serial analysis of gene expression. Science 270, 484–487.

    Article  CAS  Google Scholar 

  146. Velculescu, V. E., et al. (1997) Characterization of the yeast transcriptome. Cell 88, 243–251.

    Article  CAS  Google Scholar 

  147. Southern, E. M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J.Mol. Biol. 98, 503–517.

    Article  CAS  Google Scholar 

  148. Southern, E., Mir, K., and Shchepinov, M. (1999) Molecular interactions on microarrays. Nat. Genet. 21(suppl), 5–9.

    Article  CAS  Google Scholar 

  149. Schena, M., et al. (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467–470.

    Article  CAS  Google Scholar 

  150. Duggan, D. J., et al. (1999) Expression profiling using cDNA microarrays. Nat. Genet. 21(suppl), 10–14.

    Article  CAS  Google Scholar 

  151. Cheung, V. G., et al. (1999) Making and reading microarrays. Nat. Genet. 21(suppl), 15–19.

    Article  CAS  Google Scholar 

  152. Bowtell, D. D. (1999) Options available-from start to finish-for obtaining expression data by microarray. Nat. Genet. 21(suppl), 25–32.

    Article  CAS  Google Scholar 

  153. Lipshutz, R. J., et al. (1999) High density synthetic oligonucleotide arrays. Nat. Genet. 21(suppl), 20–24.

    Article  CAS  Google Scholar 

  154. Hughes, T. R., et al. (2001) Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nat. Biotechnol. 19, 342–347.

    Article  CAS  Google Scholar 

  155. Eisen, M. B., et al. (1998) Cluster analysis and display of genome-wide expression patterns. Proc. Natl. Acad. Sci. USA 95, 14,863–14,868.

    Article  CAS  Google Scholar 

  156. Baker, T. K., et al. (2001) Temporal gene expression analysis of monolayer cultured rat hepatocytes. Chem. Res. Toxicol. 14, 1218–1231.

    Article  CAS  Google Scholar 

  157. Gullans, S. R. (2000) Of microarrays and meandering data points. Nat. Genet. 26, 4–5.

    Article  CAS  Google Scholar 

  158. Tusher, V. G., Tibshirani, R., and Chu, G. (2001) Significance analysis of microarrays applied to the ionizing radiation response. (erratum appears in Proc. Natl. Acad. Sci. USA 2001 Aug 28;98,10515). Proc. Natl. Acad. Sci. USA 98, 5116–5121.

    Article  CAS  Google Scholar 

  159. Zhao, L. P., Prentice, R., and Breeden, L. (2001) Statistical modeling of large microarray data sets to identify stimulus-response profiles. Proc. Natl. Acad. Sci. USA 98, 5631–5636.

    Article  CAS  Google Scholar 

  160. Kerr, M. K. and Churchill, G. A. (2001) Statistical design and the analysis of gene expression microarray data. Genet. Res. 77, 123–128.

    CAS  Google Scholar 

  161. Kerr, M. K. and Churchill, G. A. (2001) Bootstrap** cluster analysis, assessing the reliability of conclusions from microarray experiments. Proc. Natl. Acad. Sci. USA 98, 8961–8965.

    Article  CAS  Google Scholar 

  162. Siedow, J. N. (2001) Making sense of microarrays. Genome Biol 2, 4003.

    Article  Google Scholar 

  163. Brazma, A., et al. (2001) Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat. Genet. 29, 365–371.

    Article  CAS  Google Scholar 

  164. Decottignies, A. and Goffeau, A. (1997) Complete inventory of the yeast ABC proteins. Nat. Genet. 15, 137–145.

    Article  CAS  Google Scholar 

  165. Tatusov, R. L., Koonin, E. V., and Lipman, D. J. (1997) A genomic perspective on protein families. Science 278, 631–637.

    Article  CAS  Google Scholar 

  166. Lockhart, D. J. (1998) Mutant yeast on drugs. Nat. Med. 4, 1235–1236.

    Article  CAS  Google Scholar 

  167. Oliver, S. (1999) Redundancy reveals drugs in action. Nat. Genet. 21, 245–246.

    Article  CAS  Google Scholar 

  168. Marton, M. J., et al. (1998) Drug target validation and identification of secondary drug target effects using DNA microarrays. Nat. Med. 4, 1293–1301.

    Article  CAS  Google Scholar 

  169. Gray, N. S., et al. (1998) Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science 281, 533–538.

    Article  CAS  Google Scholar 

  170. Corder, E. H., et al. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261, 921–923.

    Article  CAS  Google Scholar 

  171. Saunders, A. M., et al. (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 43, 1467–1472.

    Article  CAS  Google Scholar 

  172. Farlow, M. R., et al. (1996) Apolipoprotein E genotype and gender influence response to tacrine therapy. Annu. NY Acad. Sci. 802, 101–110.

    Article  CAS  Google Scholar 

  173. Altshuler, D., et al. (2000) The common PPARgamma Prol2Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat. Genet. 26, 76–80.

    Article  CAS  Google Scholar 

  174. Drazen, J. M., et al. (1999) Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat. Genet. 22, 168–170.

    Article  CAS  Google Scholar 

  175. Liggett, S. B. (2001) Pharmacogenetic applications of the human genome project. Nat. Med. 7, 281–283.

    Article  CAS  Google Scholar 

  176. Debouck, C. and Goodfellow, N. (1999) DNA microarrays in drug discovery and development. Nat. Genet. 21(suppl), 48–50.

    Article  CAS  Google Scholar 

  177. Glynne, R., et al. (2000) B-lymphocyte quiescence, tolerance and activation as viewed by global gene expression profiling on microarrays. Immunol. Rev. 176, 216–246.

    Article  CAS  Google Scholar 

  178. Glynne, R., et al. (2000) How self-tolerance and the immunosuppressive drug FK506 prevent B-cell mitogenesis. Nature 403, 672–676.

    Article  CAS  Google Scholar 

  179. Ross, D. T., et al. (2000) Systematic variation in gene expression patterns in human cancer cell lines. Nat. Genet. 24, 227–235.

    Article  CAS  Google Scholar 

  180. Scherf, U., et al. (2000) A gene expression database for the molecular pharmacology of cancer. Nat. Genet. 24, 236–244.

    Article  CAS  Google Scholar 

  181. Pinkel, D. (2000) Cancer cells, chemotherapy and gene clusters. Nat. Genet. 24, 208–209.

    Article  CAS  Google Scholar 

  182. Wang, W., et al. (2001) Pharmacogenomic dissection of resistance to thymidylate synthase inhibitors. Cancer Res. 61, 5505–5510.

    CAS  Google Scholar 

  183. Lam, L. T., et al. (2001) Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol. 2, 0041.

    Article  Google Scholar 

  184. Der, S. D., et al. (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc. Natl. Acad. Sci. USA 95, 15,623–15,628.

    Article  CAS  Google Scholar 

  185. Garber, K. (2000) Protein C may be sepsis solution. Nat. Biotechnol. 18, 917–918.

    Article  CAS  Google Scholar 

  186. Grinnell, B. W. and Joyce, D. (2001) Recombinant human activated protein C, a system modulator of vascular function for treatment of severe sepsis. Crit. Care Med. 29(suppl), S53–S60; discussion S60–S61.

    Article  CAS  Google Scholar 

  187. Joyce, D. E., et al. (2001) Gene expression profile of antithrombotic protein c defines new mechanisms modulating inflammation and apoptosis. J.Biol. Chem. 276, 11,199–11,203.

    Article  CAS  Google Scholar 

  188. DeFrancesco, L. (2001) First sepsis drug nears market. Nat. Med. 7, 516–517.

    Article  CAS  Google Scholar 

  189. Golub, T. R., et al. (1999) Molecular classification of cancer, class discovery and class prediction by gene expression monitoring. Science 286, 531–537.

    Article  CAS  Google Scholar 

  190. Sorlie, T., et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. USA 98, 10,869–10,874.

    Article  CAS  Google Scholar 

  191. Hammond, T. G., et al. (2000) Mechanical culture conditions effect gene expression, gravityinduced changes on the space shuttle. Physiol. Genomics 3, 163–173.

    CAS  Google Scholar 

  192. Chen, B. P., et al. (2001) DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Physiol. Genomics 7, 55–63.

    Article  CAS  Google Scholar 

  193. DeRisi, J. L., Iyer, V. R., and Brown, O. (1997) Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278, 680–686.

    Article  CAS  Google Scholar 

Download references

Authors
  1. Lawrence M. Gelbert
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Eli Lilly and Company, Indianapolis, IN, USA

    Victor A. Vinci PhD

  2. Dow AgroSciences, Indianapolis, IN, USA

    Sarad R. Parekh PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Gelbert, L.M. (2003). Genome Sequencing and Genomic Technologies in Drug Discovery and Development. In: Vinci, V.A., Parekh, S.R. (eds) Handbook of Industrial Cell Culture. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-346-0_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-346-0_13

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-315-2

  • Online ISBN: 978-1-59259-346-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation