Mammalian Genome

, Volume 17, Issue 6, pp 643–656 | Cite as

How replicable are mRNA expression QTL?

  • Jeremy L. Peirce
  • Hongqiang Li
  • Jintao Wang
  • Kenneth F. Manly
  • Robert J. Hitzemann
  • John K. Belknap
  • Glenn D. Rosen
  • Shirlean Goodwin
  • Thomas R. Sutter
  • Robert W. Williams
  • Lu Lu
Article

Abstract

Applying quantitative trait analysis methods to genome-wide microarray-derived mRNA expression phenotypes in segregating populations is a valuable tool in the attempt to link high-level traits to their molecular causes. The massive multiple-testing issues involved in analyzing these data make the correct level of confidence to place in mRNA abundance quantitative trait loci (QTL) a difficult problem. We use a unique resource to directly test mRNA abundance QTL replicability in mice: paired recombinant inbred (RI) and F2 data sets derived from C57BL/6J (B6) and DBA/2J (D2) inbred strains and phenotyped using the same Affymetrix arrays. We have one forebrain and one striatum data set pair. We describe QTL replication at varying stringencies in these data. For instance, 78% of mRNA expression QTL (eQTL) with genome-wide adjusted p ≤ 0.0001 in RI data replicate at a genome-wide adjusted p < 0.05 or better. Replicated QTL are disproportionately putatively cis-acting, and approximately 75% have higher apparent expression levels associated with B6 genotypes, which may be partly due to probe set generation using B6 sequence. Finally, we note that while trans-acting QTL do not replicate well between data sets in general, at least one cluster of trans-acting QTL on distal Chr 1 is notably preserved between data sets.

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Jeremy L. Peirce
    • 1
    • 2
  • Hongqiang Li
    • 1
    • 2
  • Jintao Wang
    • 3
  • Kenneth F. Manly
    • 2
    • 3
    • 4
  • Robert J. Hitzemann
    • 5
  • John K. Belknap
    • 5
  • Glenn D. Rosen
    • 6
  • Shirlean Goodwin
    • 7
  • Thomas R. Sutter
    • 7
  • Robert W. Williams
    • 1
    • 2
  • Lu Lu
    • 1
    • 2
    • 8
  1. 1.Center for Neuroscience, Department of Anatomy and NeurobiologyUniversity of Tennessee Health Science CenterMemphisUSA
  2. 2.Center for Genomics and Bioinformatics, Department of Anatomy and NeurobiologyUniversity of Tennessee Health Science CenterMemphisUSA
  3. 3.Department of Anatomy and NeurobiologyUniversity of Tennessee Health Science CenterMemphisUSA
  4. 4.Department of Pathology and Laboratory MedicineUniversity of Tennessee Health Science CenterMemphisUSA
  5. 5.Portland Alcohol Research Center, Department of Behavioral NeuroscienceOregon Health & Science UniversityPortlandUSA
  6. 6.Department of NeurologyBeth Israel Deaconess Medical CenterBostonUSA
  7. 7.W. Harry Feinstone Center for Genomic ResearchUniversity of MemphisMemphisUSA
  8. 8.Key Laboratory of Nerve Regeneration in Jiangsu ProvinceNantong UniversityNantongChina

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