Skip to main content

Advertisement

Log in

Moderne genetische Analysemethoden

Grundlagen für eine genetisch basierte Prävention

Current methods in genetic analysis

An approach for genetics-based preventive medicine

  • Leitthema
  • Published:
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz Aims and scope

Zusammenfassung

Moderne genetische Analysemethoden wie DNA-Arrays (Gen-Chips) oder Hochdurchsatz-DNA-Sequenzanalyseverfahren der nächsten Generation (Next Generation Sequencing, NGS) haben in den vergangenen 10 Jahren der „Postgenom-Ära“ das hohe Innovationstempo, das durch die Genomforschung vorgegeben wurde, nochmals erheblich erhöht. In der vorliegenden Arbeit werden mit den Array- und NGS-Verfahren zwei wichtige innovationstreibende Methoden und Beispiele für deren Anwendung in wissenschaftlichen Großprojekten vorgestellt. Eine breite Anwendung dieser sehr leistungsfähigen Technologien für genetische Reihenuntersuchungen zum Zwecke der Krankheitsprävention ist derzeit jedoch noch nicht in Sicht. Der Komplexitätsgrad der Interaktion zwischen Genen, Genprodukten und Umwelt hat alle Erwartungen übertroffen, sodass zuverlässige Aussagen über die medizinische Relevanz häufiger genetischer Varianten derzeit nur in wenigen Bereichen wie z. B. der Pharmakogenetik oder der Onkologie möglich sind. Es werden auch ethische Fragen diskutiert, die durch ein genetisches Bevölkerungsscreening aufgeworfen werden. Ziel des Beitrags ist es, über einen kurzen Abriss der Methodenentwicklung in der Molekulargenetik zu den heute dominierenden modernen Technologien überzuleiten und deren Anwendungen in der Forschung und der Diagnostik von seltenen Krankheiten, auch im Hinblick auf Screeningansätze, darzustellen.

Abstract

Modern genetic analysis methods such as DNA arrays (gene chips) or high-throughput DNA sequencing of the next generation (Next Generation Sequencing, NGS) have once again accelerated the pace of innovation that has been powered by genome research over the past 10 years of the “post-genomic era”. The present paper introduces array and NGS methods as two important innovation driving methods and provides examples for their application in large-scale scientific projects. However, a broad application of these very powerful technologies for genetic screening for the purpose of disease prevention is currently not yet in sight. The complexity of the interaction of genes, gene products and the environment has so far exceeded all expectations, suggesting that reliable statements about the medical relevance of common genetic variants can presently only be made in a few areas such as pharmacogenetics and oncology. We also discuss ethical issues raised by genetic population screening. The aim of this paper is to provide a brief outline of the development of methods in molecular genetics to the now dominant modern technologies and present their applications in research, in the diagnosis of rare diseases, and in terms of screening approaches.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Venter JC, Adams M, Myers E et al (2001) The sequence of the human genome. Science 291:1304–1351

    Article  CAS  PubMed  Google Scholar 

  2. Lander ES, Linton LM, Birren B et al (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  CAS  PubMed  Google Scholar 

  3. Saiki RK, Scharf S, Faloona F, Horn GT, Erlich HA, Arnheim N (1985) Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230:1350–1354

    Article  CAS  PubMed  Google Scholar 

  4. Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci 74:5463–5467

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Hood LE, Hunkapiller MW, Smith LM (1987) Automated DNA sequencing and analysis of the human genome. Genomics 1(3):201–212

    Article  CAS  PubMed  Google Scholar 

  6. Palca J (1988) James Watson to head NIH human genome project. Nature 335:193

    CAS  PubMed  Google Scholar 

  7. Fodor SP, Read JL, Pirrung MC, Stryer L, Lu AT, Solas D (1991) Light-directed, spatially addressable parallel chemical synthesis. Science 251:767–773

    Article  CAS  PubMed  Google Scholar 

  8. Klein H-G (2005) Editorial: 10 Jahre Microarrays – Meilensteine für die Genomanalyse/10 years of microarrays – milestones for genomic analyis. LaboratoriumsMedizin, 28:205

    Article  Google Scholar 

  9. Sayers EW, Barrett T, Benson DA et al (2011) Database resources of the National Center for Biotechnology Information. Nucl Acid Res 39:D38–51

    Article  CAS  Google Scholar 

  10. Kallioniemi A, Kallioniemi OP, Sudar Da, Rutovitz D, Gray JW, Waldman F, Pinkel D (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science 258:818–821

    Article  CAS  PubMed  Google Scholar 

  11. du Manoir S, Speicher MR, Joos S, Schröck E, Popp S, Döhner H, Kovacs G, Robert-Nicoud M, Lichter P, Cremer T (1993) Detection of complete and partial chromosome gains and losses by comparative genomic in situ hybridization. Human Genetics 90:590–610

    Article  CAS  PubMed  Google Scholar 

  12. Snijders AM, Nowak N, Segraves R, Blackwood S, Brown N, Conroy J, Hamilton G, Hindle AK, Huey B, Kimura K, Law S, Myambo K, Palmer J, Ylstra B, Yue JP, Gray JW, Jain AN, Pinkel D, Albertson DG (2001) Assembly of microarrays for genome-wide measurement of DNA copy number. Nature Genet 29:263–264

    Article  CAS  PubMed  Google Scholar 

  13. Heinrich U, Rost I, Brown A, Gordon T, Haan N, Massie J (2009) Array comparative genomic hybridisation in clinical diagnostics: principles and applications/Array-CGH in der klinischen Diagnostik: Prinzipien und Anwendungen. J Lab Med 33:355–355

    Google Scholar 

  14. Heid AK (2013) International trends influencing the health economic landscape. The Wharton School, Univ of Pennsylvania, Philadelphia und Karlsruher Institut für Technologie, Masterarbeit. www.archives.upenn.edu

  15. Davis, JC (2009) The microeconomics of personalized medicine: today’s challenge and tomorrow’s promise. Nat Rev Drug Discov 8:279–286

    Article  CAS  PubMed  Google Scholar 

  16. Bader J, Hammond R W, Henck SA, Deem MW, McDermott GA, Bustillo JM, Simpson JW, Mulhern GT, Rothberg JM (1999) DNA transport by a micromachined Brownian ratchet device. PNAS USA 96:13165–13169

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Klein HG, Bauer P, Hambuch T (2014) Whole genome sequencing (WGS), whole exome sequencing (WES) and clinical exome sequencing (CES) in patient care. J Lab Med 38:211

    Google Scholar 

  18. The International HapMap Consortium (2003) The International HapMap Project. Nature 426:789–796

    Article  Google Scholar 

  19. ENCODE Project Consortium (2004) The ENCODE (ENCylopedia Of DNA Elements) Project. Science 306:636–640

    Article  Google Scholar 

  20. The 1000 Genomes Project Consortium (2010) A map of human genome variation from population-scale sequencing. Nature 467:1061

    Article  PubMed Central  Google Scholar 

  21. http://www.ICGC.org

  22. http://www.genetik-gesundheit.de/PHG/Das_Projekt

  23. http://www.gfhev.de/de/leitlinien/gfh.htm#position. (2007)

  24. Bundesgesetzblatt (2009) BGBl. I S. 2529, ber. 3672

  25. Heidemann S, Schillhorn K (2011) Gendiagnostikgesetz: Kommentar für die Praxis. Gesundheitswesen in der Praxis. Medhochzwei, Heidelberg

  26. Kirchheiner J (2004) Arzneitherapieempfehlungen auf pharmakogenetischer Basis. Habilitationsschrift zur Klinischen Pharmakologie, Medizinische Fakultät der Charité, Berlin

  27. http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures. in vitro Diagnostics

  28. Grumbt B, Eck SH, Hinrichsen T, Hirv K (2013) Diagnostic applications of next generation sequencing in immunogenetics and molecular oncology. Transfus Med Hemother 40:196–206

    Article  PubMed Central  PubMed  Google Scholar 

  29. Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE, Mudge J, Langley RJ, Zhang L, Lee CC, Schilkey FD, Sheth V, Woodward JE, Peckham HE, Schroth GP, Kim RW, Kingsmore SF (2011) Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med 3:65

    Article  Google Scholar 

  30. Henn, M et al (2007) In Humangenetik: Die wichtigsten Antworten. Herder Spektrum, Freiburg

  31. Liebl B, Roscher AA (1998) Neonatal screening for congenital metabolic disorders in Bavaria-assessment of current status and planned reorganization. Gesundheitswesen 60(Suppl 1):S20–S23

    PubMed  Google Scholar 

  32. Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A, Alnadi NA, Andraws N, Patterson ML, Krivohlavek LA, Fellis J, Humphray S, Saffrey P, Kingsbury Z, Weir JC, Betley J, Grocock RJ, Margulies EH, Farrow EG, Artman M, Safina NP, Petrikin JE, Hall KP, Kingsmore SF (2012) Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci Transl Med 4:154ra135

    Article  PubMed Central  PubMed  Google Scholar 

  33. Goldenberg AJ, Sharp RR (2012) The ethical hazards and programmatic challenges of genomic newborn screening. JAMA 307:461–462

    Article  PubMed  Google Scholar 

  34. Swenson LC, Däumer M, Paredes R (2012) Next-generation sequencing to assess HIV tropism. Curr Opin HIV AIDS 7:478–485

    Article  CAS  PubMed  Google Scholar 

  35. Vogel G (2014) Infectious disease. Genomes reveal start of Ebola outbreak. Science 345:989–990

    Article  CAS  PubMed  Google Scholar 

  36. de La Vega FM, Bustamante CD, Leal SM (2011) Genome-wide association mapping and rare alleles: from population genomics to personalized medicine. Pac Symp Biocomput 2011:74–75

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hans-Georg Klein.

Ethics declarations

Interessenkonflikt

H.-G. Klein und I. Rost erklären keinen Interessenkonflikt.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Klein, HG., Rost, I. Moderne genetische Analysemethoden. Bundesgesundheitsbl. 58, 113–120 (2015). https://doi.org/10.1007/s00103-014-2088-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00103-014-2088-z

Schlüsselwörter

Keywords

Navigation