Gastroenterology
Volume 129, Issue 5 , Pages 1720-1752 , November 2005

American Gastroenterological Association Future Trends Committee Report: The Application of Genomic and Proteomic Technologies to Digestive Disease Diagnosis and Treatment and Their Likely Impact on Gastroenterology Clinical Practice

  • Konstantinos N. Lazaridis

      Affiliations

    • Corresponding Author InformationAddress requests for reprints to: Chair, Future Trends Committee, AGA National Office, c/o Membership Department, 4930 Del Ray Avenue, Bethesda, Maryland 20814. Fax: (301) 654-5920.
    • ,
  • Brian D. Juran

      Affiliations

    • Corresponding Author InformationAddress requests for reprints to: Chair, Future Trends Committee, AGA National Office, c/o Membership Department, 4930 Del Ray Avenue, Bethesda, Maryland 20814. Fax: (301) 654-5920.

References 

  1. Varmus H . Getting ready for gene-based medicine . N Engl J Med . 2002;347:1526–1527
  2. Watson JD , Crick FH . Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid . Nature . 1953;171:737–738
  3. 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
  4. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome . Science . 2001;291:1304–1351
  5. Guttmacher AE , Collins FS . Welcome to the genomic era . N Engl J Med . 2003;349:996–998
  6. Collins FS . The human genome project and the future of medicine . Ann N Y Acad Sci . 1999;882:42–55 discussion 56–65
  7. Guttmacher AE , Collins FS . Genomic medicine—a primer . N Engl J Med . 2002;347:1512–1520
  8. Posadas EM , Simpkins F , Liotta LA , MacDonald C , Kohn EC . Proteomic analysis for the early detection and rational treatment of cancer—realistic hope? . Ann Oncol . 2005;16:16–22
  9. Kaprio J . Science, medicine, and the future (genetic epidemiology) . BMJ . 2000;320:1257–1259
  10. Altman RB . Bioinformatics in support of molecular medicine . Proc AMIA Symp . 1998;53–61
  11. Kruglyak L , Nickerson DA . Variation is the spice of life . Nat Genet . 2001;27:234–236
  12. Collins FS , Guyer MS , Chakravarti A . Variations on a theme (cataloging human DNA sequence variation) . Science . 1997;278:1580–1581
  13. Lee C . Irresistible force meets immovable object (SNP mapping of complex diseases) . Trends Genet . 2002;18:67–69
  14. Tabor HK , Risch NJ , Myers RM . Opinion: candidate-gene approaches for studying complex genetic traits: practical considerations . Nat Rev Genet . 2002;3:391–397
  15. Pritchard JK . Are rare variants responsible for susceptibility to complex diseases? . Am J Hum Genet . 2001;69:124–137
  16. Weiss KM , Terwilliger JD . How many diseases does it take to map a gene with SNPs? . Nat Genet . 2000;26:151–157
  17. Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P, et al. A second-generation linkage map of the human genome . Nature . 1992;359:794–801
  18. Schlotterer C . The evolution of molecular markers—just a matter of fashion? . Nat Rev Genet . 2004;5:63–69
  19. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease . Nature . 2001;411:599–603
  20. Stumpf MPH . Haplotype diversity and the block structure of linkage disequilibrium . Trends Genet . 2002;18:226–228
  21. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, et al. The structure of haplotype blocks in the human genome . Science . 2002;296:2225–2229
  22. Cardon LR , Abecasis GR . Using haplotype blocks to map human complex trait loci . Trends Genet . 2003;19:135–140
  23. Lavorgna G , Dahary D , Lehner B , Sorek R , Sanderson CM , Casari G . In search of antisense . Trends Biochem Sci . 2004;29:88–94
  24. Morey C , Avner P . Employment opportunities for non-coding RNAs . FEBS Lett . 2004;567:27–34
  25. Heard E . Recent advances in X-chromosome inactivation . Curr Opin Cell Biol . 2004;16:247–255
  26. Wulfkuhle J , Espina V , Liotta L , Petricoin E . Genomic and proteomic technologies for individualisation and improvement of cancer treatment . Eur J Cancer . 2004;40:2623–2632
  27. Petricoin EF , Fishman DA , Conrads TP , Veenstra TD , Liotta LA . Lessons from Kitty Hawk (from feasibility to routine clinical use for the field of proteomic pattern diagnostics) . Proteomics . 2004;4:2357–2360
  28. Espina V, Mehta AI, Winters ME, Calvert V, Wulfkuhle J, Petricoin EF, et al. Protein microarrays (molecular profiling technologies for clinical specimens) . Proteomics . 2003;3:2091–2100
  29. Orchard S, Hermjakob H, Binz PA, Hoogland C, Taylor CF, Zhu W, et al. Further steps towards data standardisation (the Proteomic Standards Initiative HUPO 3(rd) annual congress, Beijing 25–27(th) October, 2004) . Proteomics . 2005;5:337–339
  30. Ruddle FH . The William Allan Memorial Award address (reverse genetics and beyond) . Am J Hum Genet . 1984;36:944–953
  31. Royer-Pokora B, Kunkel LM, Monaco AP, Goff SC, Newburger PE, Baehner RL, et al. Cloning the gene for an inherited human disorder—chronic granulomatous disease—on the basis of its chromosomal location . Nature . 1986;322:32–38
  32. Cargill M , Daley GQ . Mining for SNPs (putting the common variants—common disease hypothesis to the test) . Pharmacogenomics . 2000;1:27–37
  33. Collins FS , Green ED , Guttmacher AE , Guyer MS . A vision for the future of genomics research . Nature . 2003;422:835–847
  34. Ghosh S , Collins FS . The geneticist’s approach to complex disease . Annu Rev Med . 1996;47:333–353
  35. Romero R , Kuivaniemi H , Tromp G , Olson JM . The design, execution, and interpretation of genetic association studies to decipher complex diseases . Am J Obstet Gynecol . 2002;187:1299–1312
  36. Devlin B , Roeder K . Genomic control for association studies . Biometrics . 1999;55:997–1004
  37. Hirschhorn JN , Altshuler D . Once and again—issues surrounding replication in genetic association studies . (editorial) J Clin Endocrinol Metab . 2002;87:4438–4441
  38. Hirschhorn JN , Daly MJ . Genome-wide association studies for common diseases and complex traits . Nat Rev Genet . 2005;6:95–108
  39. Wang W , Barratt BJ , Clayton DG , Todd JA . Genome-wide association studies (theoretical and practical concerns) . Nat Rev Genet . 2005;6:109–118
  40. Schaid DJ . Likelihoods and TDT for the case-parents design . Genet Epidemiol . 1999;16:250–260
  41. Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, et al  Identification and characterization of the familial adenomatous polyposis coli gene . Cell . 1991;66:589–600
  42. Kinzler KW , Vogelstein B . Lessons from hereditary colorectal cancer . Cell . 1996;87:159–170
  43. Beroud C , Collod-Beroud G , Boileau C , Soussi T , Junien C . UMD (universal mutation database) (a generic software to build and analyze locus-specific databases) . Hum Mutat . 2000;15:86–94
  44. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis . Nat Genet . 1996;13:399–408
  45. Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, Breuning MH, et al. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis . Nat Genet . 2001;28:213–214
  46. Camaschella C, Roetto A, Cali A, De Gobbi M, Garozzo G, Carella M, et al. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22 . Nat Genet . 2000;25:14–15
  47. Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dube MP, et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis . Nat Genet . 2004;36:77–82
  48. Yamashita C , Adams PC . Natural history of the C282Y homozygote for the hemochromatosis gene (HFE) with a normal serum ferritin level . Clin Gastroenterol Hepatol . 2003;1:388–391
  49. Andersen RV , Tybjaerg-Hansen A , Appleyard M , Birgens H , Nordestgaard BG . Hemochromatosis mutations in the general population (iron overload progression rate) . Blood . 2004;103:2914–2919
  50. Bacon BR . Hemochromatosis (diagnosis and management) . Gastroenterology . 2001;120:718–725
  51. Petrukhin K, Fischer SG, Pirastu M, Tanzi RE, Chernov I, Devoto M, et al  Mapping, cloning and genetic characterization of the region containing the Wilson disease gene . Nat Genet . 1993;5:338–343
  52. Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, et al  The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene . Nat Genet . 1993;5:344–350
  53. Lutsenko S , Petris MJ . Function and regulation of the mammalian copper-transporting ATPases (insights from biochemical and cell biological approaches) . J Membr Biol . 2003;191:1–12
  54. Tysk C , Lindberg E , Jarnerot G , Floderus-Myrhed B . Ulcerative colitis and Crohn’s disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking . Gut . 1988;29:990–996
  55. Roth MP , Petersen GM , McElree C , Vadheim CM , Panish JF , Rotter JI . Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews . Gastroenterology . 1989;96:1016–1020
  56. Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, et al. Mapping of a susceptibility locus for Crohn’s disease on chromosome 16 . Nature . 1996;379:821–823
  57. Zheng CQ , Hu GZ , Lin LJ , Gu GG . Progress in searching for susceptibility gene for inflammatory bowel disease by positional cloning . World J Gastroenterol . 2003;9:1646–1656
  58. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease . Nature . 2001;411:603–606
  59. van der Linde K , Boor PP , Houwing-Duistermaat JJ , Kuipers EJ , Wilson JH , de Rooij FW . Card15 and Crohn’s disease (healthy homozygous carriers of the 3020insC frameshift mutation) . Am J Gastroenterol . 2003;98:613–627
  60. Ahmad T , Tamboli CP , Jewell D , Colombel JF . Clinical relevance of advances in genetics and pharmacogenetics of IBD . Gastroenterology . 2004;126:1533–1549
  61. Satsangi J, Parkes M, Louis E, Hashimoto L, Kato N, Welsh K, et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12 . Nat Genet . 1996;14:199–202
  62. Satsangi J, Welsh KI, Bunce M, Julier C, Farrant JM, Bell JI, et al. Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease . Lancet . 1996;347:1212–1217
  63. Ma Y, Ohmen JD, Li Z, Bentley LG, McElree C, Pressman S, et al. A genome-wide search identifies potential new susceptibility loci for Crohn’s disease . Inflamm Bowel Dis . 1999;5:271–278
  64. Rioux JD, Daly MJ, Silverberg MS, Lindblad K, Steinhart H, Cohen Z, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease . Nat Genet . 2001;29:223–228
  65. Malaty HM , Engstrand L , Pedersen NL , Graham DY . Helicobacter pylori infection: genetic and environmental influences. A study of twins . Ann Intern Med . 1994;120:982–986
  66. Thye T , Burchard GD , Nilius M , Muller-Myhsok B , Horstmann RD . Genome wide linkage analysis identifies polymorphism in the human interferon-γ receptor affecting Helicobacter pylori infection . Am J Hum Genet . 2003;72:448–453
  67. Drovdlic CM, Goddard KA, Chak A, Brock W, Chessler L, King JF, et al. Demographic and phenotypic features of 70 families segregating Barrett’s oesophagus and oesophageal adenocarcinoma . J Med Genet . 2003;40:651–656
  68. Gelfand MD . Barrett esophagus in sexagenarian identical twins . J Clin Gastroenterol . 1983;5:251–253
  69. Winters C, Spurling TJ, Chobanian SJ, Curtis DJ, Esposito RL, Hacker JF, et al  Barrett’s esophagus. A prevalent, occult complication of gastroesophageal reflux disease . Gastroenterology . 1987;92:118–124
  70. Bortolotti M . Natural history of gastro-oesophageal reflux disease (the neglected factor) . Scand J Gastroenterol . 2003;38:1204–1208
  71. Romero Y, Cameron AJ, Locke GR, Schaid DJ, Slezak JM, Branch CD, et al. Familial aggregation of gastroesophageal reflux in patients with Barrett’s esophagus and esophageal adenocarcinoma . Gastroenterology . 1997;113:1449–1456
  72. Cameron AJ , Lagergren J , Henriksson C , Nyren O , Locke GR , Pedersen NL . Gastroesophageal reflux disease in monozygotic and dizygotic twins . Gastroenterology . 2002;122:55–59
  73. Hu FZ, Preston RA, Post JC, White GJ, Kikuchi LW, Wang X, et al. Mapping of a gene for severe pediatric gastroesophageal reflux to chromosome 13q14 . JAMA . 2000;284:325–334
  74. Not T, Horvath K, Hill ID, Partanen J, Hammed A, Magazzu G, et al. Celiac disease risk in the USA (high prevalence of antiendomysium antibodies in healthy blood donors) . Scand J Gastroenterol . 1998;33:494–498
  75. Greco L, Romino R, Coto I, Di Cosmo N, Percopo S, Maglio M, et al. The first large population based twin study of coeliac disease . Gut . 2002;50:624–628
  76. Maki M, Holm K, Lipsanen V, Hallstrom O, Viander M, Collin P, et al. Serological markers and HLA genes among healthy first-degree relatives of patients with coeliac disease . Lancet . 1991;338:1350–1353
  77. Spurkland A, Sollid LM, Ronningen KS, Bosnes V, Ek J, Vartdal F, et al. Susceptibility to develop celiac disease is primarily associated with HLA-DQ alleles . Hum Immunol . 1990;29:157–165
  78. Polvi A, Arranz E, Fernandez-Arquero M, Collin P, Maki M, Sanz A, et al. HLA-DQ2-negative celiac disease in Finland and Spain . Hum Immunol . 1998;59:169–175
  79. Liu J, Juo SH, Holopainen P, Terwilliger J, Tong X, Grunn A, et al. Genomewide linkage analysis of celiac disease in Finnish families . Am J Hum Genet . 2002;70:51–59
  80. Zhong F, McCombs CC, Olson JM, Elston RC, Stevens FM, McCarthy CF, et al. An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland . Nat Genet . 1996;14:329–333
  81. Greco L, Corazza G, Babron MC, Clot F, Fulchignoni-Lataud MC, Percopo S, et al  Genome search in celiac disease . Am J Hum Genet . 1998;62:669–675
  82. Greco L, Babron MC, Corazza GR, Percopo S, Sica R, Clot F, et al. Existence of a genetic risk factor on chromosome 5q in Italian coeliac disease families . Ann Hum Genet . 2001;65:35–41
  83. King AL, Yiannakou JY, Brett PM, Curtis D, Morris MA, Dearlove AM, et al. A genome-wide family-based linkage study of coeliac disease . Ann Hum Genet . 2000;64:479–490
  84. Whorwell PJ , McCallum M , Creed FH , Roberts CT . Non-colonic features of irritable bowel syndrome . Gut . 1986;27:37–40
  85. Locke GR , Zinsmeister AR , Talley NJ , Fett SL , Melton LJ . Familial association in adults with functional gastrointestinal disorders . Mayo Clin Proc . 2000;75:907–912
  86. Morris-Yates A , Talley NJ , Boyce PM , Nandurkar S , Andrews G . Evidence of a genetic contribution to functional bowel disorder . Am J Gastroenterol . 1998;93:1311–1317
  87. Levy RL , Jones KR , Whitehead WE , Feld SI , Talley NJ , Corey LA . Irritable bowel syndrome in twins (heredity and social learning both contribute to etiology) . Gastroenterology . 2001;121:799–804
  88. Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region . Science . 1996;274:1527–1531
  89. Prather CM , Camilleri M , Zinsmeister AR , McKinzie S , Thomforde G . Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome . Gastroenterology . 2000;118:463–468
  90. Viramontes BE , Camilleri M , McKinzie S , Pardi DS , Burton D , Thomforde GM . Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome . Am J Gastroenterol . 2001;96:2671–2676
  91. Camilleri M, Atanasova E, Carlson PJ, Ahmad U, Kim HJ, Viramontes BE, et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome . Gastroenterology . 2002;123:425–432
  92. Pata C , Erdal ME , Derici E , Yazar A , Kanik A , Ulu O . Serotonin transporter gene polymorphism in irritable bowel syndrome . Am J Gastroenterol . 2002;97:1780–1784
  93. Yeo A, Boyd P, Lumsden S, Saunders T, Handley A, Stubbins M, et al. Association between a functional polymorphism in the serotonin transporter gene and diarrhoea predominant irritable bowel syndrome in women . Gut . 2004;53:1452–1458
  94. Kim HJ, Camilleri M, Carlson PJ, Cremonini F, Ferber I, Stephens D, et al. Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders . Gut . 2004;53:829–837
  95. Tooke N , Pettersson M . CpG methylation in clinical studies (utility, methods, and quality assurance) . IVDT . 2004;
  96. Berg LM , Sanders R , Alderborn A . Pyrosequencing technology and the need for versatile solutions in molecular clinical research . Expert Rev Mol Diagn . 2002;2:361–369
  97. Tang K , Fu DJ , Julien D , Braun A , Cantor CR , Koster H . Chip-based genotyping by mass spectrometry . Proc Natl Acad Sci U S A . 1999;96:10016–10020
  98. Hardenbol P, Baner J, Jain M, Nilsson M, Namsaraev EA, Karlin-Neumann GA, et al. Multiplexed genotyping with sequence-tagged molecular inversion probes . Nat Biotechnol . 2003;21:673–678
  99. Hardenbol P, Yu F, Belmont J, Mackenzie J, Bruckner C, Brundage T, et al. Highly multiplexed molecular inversion probe genotyping (over 10,000 targeted SNPs genotyped in a single tube assay) . Genome Res . 2005;15:269–275
  100. Oliphant A , Barker DL , Stuelpnagel JR , Chee MS . Bead array technology (enabling an accurate, cost-effective approach to high-throughput genotyping) . Biotechniques . 2002;32(Suppl):S56–S61
  101. Gunderson KL, Kruglyak S, Graige MS, Garcia F, Kermani BG, Zhao C, et al. Decoding randomly ordered DNA arrays . Genome Res . 2004;14:870–877
  102. Reinders J , Lewandrowski U , Moebius J , Wagner Y , Sickmann A . Challenges in mass spectrometry-based proteomics . Proteomics . 2004;4:3686–3703
  103. Winawer S, Fletcher R, Rex D, Bond J, Burt R, Ferrucci J, et al. Colorectal cancer screening and surveillance (clinical guidelines and rationale—update based on new evidence) . Gastroenterology . 2003;124:544–560
  104. Bergquist A , Lindberg G , Saarinen S , Broome U . Increased prevalence of primary sclerosing cholangitis among first-degree relatives . J Hepatol . 2005;42:252–256
  105. Food and Drug Administration . Medical devices: clinical chemistry and clinical toxicology devices: drug metabolizing enzyme genotyping system . Fed Regist . 2005;46:11865–11867
  106. Ross JS, Schenkein DP, Kashala O, Linette GP, Stec J, Symmans WF, et al. Pharmacogenomics . Adv Anat Pathol . 2004;11:211–220
  107. Collins FS , McKusick VA . Implications of the Human Genome Project for medical science . JAMA . 2001;285:540–544
  108. Yamamoto T, Davis CG, Brown MS, Schneider WJ, Casey ML, Goldstein JL, et al. The human LDL receptor (a cysteine-rich protein with multiple Alu sequences in its mRNA) . Cell . 1984;39:27–38
  109. Pearson TA . The epidemiologic basis for population-wide cholesterol reduction in the primary prevention of coronary artery disease . Am J Cardiol . 2004;94:4F–8F
  110. Giardiello FM, Brensinger JD, Petersen GM, Luce MC, Hylind LM, Bacon JA, et al. The use and interpretation of commercial APC gene testing for familial adenomatous polyposis . N Engl J Med . 1997;336:823–827
  111. Guttmacher AE , Collins FS , Carmona RH . The family history—more important than ever . N Engl J Med . 2004;351:2333–2336
  112. Riegert-Johnson DL, Korf BR, Alford RL, Broder MI, Keats BJ, Ormond KE, et al. Outline of a medical genetics curriculum for internal medicine residency training programs . Genet Med . 2004;6:543–547

 This report was prepared by Dr. Lazaridis under the direction of the AGA Future Trends Committee. It was approved by the committee on May 15, 2005.Members of the AGA Future Trends Committee include Nicholas F. LaRusso (chair), Juan R. Malagelada, Walter J. McDonald, Pankaj J. Pasricha, Suzanne Rose, and Michael Lee Weinstein.

PII: S0016-5085(05)01209-6

doi: 10.1053/j.gastro.2005.06.047

Gastroenterology
Volume 129, Issue 5 , Pages 1720-1752 , November 2005

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