Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Relevance and limitations of public databases for microarray design: a critical approach to gene predictions

The Pharmacogenomics Journal volume 3, pages 235–241 (2003)Cite this article

ABSTRACT

In conjunction with the completion of the human genome sequence, microarray technology offers a complementary strategy to traditional methodologies used to search for genetic determinants involved in multifactorial diseases such as Alzheimer's disease. In order to gain benefits from this strategy, we have designed home-made microarrays to compare the expression of all ORFs located within loci of interest defined by genome scanning in Alzheimer family studies. Two approaches were selected using either probes amplified by PCR from a cDNA bank or specific oligonucleotides. Here, we report the challenging task of validating, prioritising and selecting the best ORFs derived from the genome sequence. The initial inventory from the NCBI website allowed us to select 5849 ORF's within nine loci. Half of them resulted from prediction models using the GenomeScan software. However, our data have shown that predicted ORFs may not be representative of exonic sequences, or even real genes. These observations have led us to exclude these ORFs from our study, decreasing their number from 5849 to 2748. Microarrays may be only ‘snapshots’ of our current knowledge of the human genome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

Abbreviations

ORF:

open reading frame

References

  1. Loring JF, Wen X, Lee JM, Seilhamer J, Somogyi R . A gene expression profile of Alzheimer's disease. DNA Cell Biol 2001; 20: 683–695.

    Article  CAS  Google Scholar 

  2. Lambert JC, Pasquier F, Cottel D, Frigard B, Amouyel P, Chartier-Harlin MC . A new polymorphism in the APOE promoter associated with the risk of developing Alzheimer's disease. Hum Mol Genet 1998; 7: 533–540.

    Article  CAS  Google Scholar 

  3. Theuns J, Van Broeckhoven C . Transcriptional regulation of Alzheimer's disease genes: implications for susceptibility. Hum Mol Genet 2000; 9: 2383–2394.

    Article  CAS  Google Scholar 

  4. Riazanskaia N, Lukiw WJ, Grigorenko A, Korovaitseva G, Dvoryanchikov G, Moliaka Y et al. Regulatory region variability in the human presenilin-2 (PSEN2) gene: potential contribution to the gene activity and risk for AD. Mol Psychiatry 2002; 7: 891–898.

    Article  CAS  Google Scholar 

  5. Wavrant-De Vrieze F, Crook R, Holmans P, Kehoe P, Owen MJ, Williams J et al. Genetic variability in the amyloid-beta precursor protein locus may contribute to the risk of late-onset Alzheimer's disease. Neurosci Lett 1999; 269: 67–70.

    Article  Google Scholar 

  6. Kehoe P, Wavrant-De Vrieze F, Crook R, Wu WS, Holmans P, Fenton I et al. A full genome scan for late onset Alzheimer's disease. Hum Mol Genet 1999; 8: 237–245.

    Article  CAS  Google Scholar 

  7. Myers A, Wavrant De-Vrieze F, Holmans P, Hamshere M, Crook R, Compton D et al. Full genome screen for Alzheimer disease: stage II analysis. Am J Med Genet 2002; 114: 235–244.

    Article  Google Scholar 

  8. Pericak-Vance MA, Grubber J, Bailey LR, Hedges D, West S, Santoro L et al. Identification of novel genes in late-onset Alzheimer's disease. Exp Gerontol 2000; 35: 1343–1352.

    Article  CAS  Google Scholar 

  9. Olson JM, Goddard KA, Dudek DM . A second locus for very-late-onset Alzheimer disease: a genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region. Am J Hum Genet 2002; 71: 154–161.

    Article  CAS  Google Scholar 

  10. Yeh RF, Lim LP, Burge CB . Computational inference of homologous gene structures in the human genome. Genome Res 2001; 11: 803–816.

    Article  CAS  Google Scholar 

  11. Pruitt KD, Maglott DR . RefSeq and LocusLink: NCBI gene-centered resources. Nucleic Acids Res 1999; 29: 137–140.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Dr Aline Meirhaeghe-Hurez and Dr David Mann for their helpful discussion. This work was supported by INSERM and the ‘Génopole de Lille’.

Author information

Authors and Affiliations

  1. Unité INSERM 508, Institut Pasteur de Lille, 1 rue du professeur Calmette, Lille cédex, France

    J-C Lambert, E Testa & P Amouyel

  2. Centre intégré de bio-informatique de la Génopole de Lille, Cité Scientifique, Villeneuve d'Ascq cédex, 59655, France

    V Cognat & J Soula

  3. Laboratoire de biopuces, Institut Pasteur de Lille, 1 rue du professeur Calmette, Lille cédex, 59019, France

    D Hot & Y Lemoine

  4. Centre national de séquençage, 2 rue Gaston Crémieux, CP 5706, Evry cédex, 91057, France

    G Gaypay

Authors
  1. J-C Lambert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Testa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V Cognat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Soula
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Hot
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y Lemoine
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G Gaypay
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P Amouyel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J-C Lambert.

Additional information

DUALITY OF INTEREST

None declared.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lambert, JC., Testa, E., Cognat, V. et al. Relevance and limitations of public databases for microarray design: a critical approach to gene predictions. Pharmacogenomics J 3, 235–241 (2003). https://doi.org/10.1038/sj.tpj.6500184

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.tpj.6500184

Keywords

This article is cited by

Search

Advanced search

Quick links