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Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids

Nature Genetics volume 40, pages 421–429 (2008)Cite this article

An Erratum to this article was published on 01 May 2008

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Abstract

We mapped regulatory loci for nearly all protein-coding genes in mammals using comparative genomic hybridization and expression array measurements from a panel of mouse–hamster radiation hybrid cell lines. The large number of breaks in the mouse chromosomes and the dense genotyping of the panel allowed extremely sharp mapping of loci. As the regulatory loci result from extra gene dosage, we call them copy number expression quantitative trait loci, or ceQTLs. The −2log10P support interval for the ceQTLs was <150 kb, containing an average of <2–3 genes. We identified 29,769 trans ceQTLs with −log10P > 4, including 13 hotspots each regulating >100 genes in trans. Further, this work identifies 2,761 trans ceQTLs harboring no known genes, and provides evidence for a mode of gene expression autoregulation specific to the X chromosome.

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Figure 1
Figure 2: CGH results.
Figure 3: Models.
Figure 4: Cis and trans ceQTLs.
Figure 5: Individual cis and trans ceQTLs.
Figure 6: Effect sizes and regulatory hotspots.
Figure 7: Trans ceQTLs lacking known genes.

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Gene Expression Omnibus

Change history

  • 28 April 2008

    In the version of this article initially published, the scale was inadvertently omitted from the bottom left portion of Figure 4. This error has been corrected in the PDF version of the article.

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Author information

Author notes

  1. Joshua S Bloom & Tongtong Wu

    Present address: Present addresses: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA (J.S.B.) and Department of Epidemiology and Biostatistics, College of Health and Human Performance, University of Maryland, College Park, Maryland 20742, USA (T.W.).,

Authors and Affiliations

  1. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 90095, California, USA

    Christopher C Park, Joshua S Bloom, Andy Lin, Richard T Wang, Aswin Sekar, Arshad H Khan & Desmond J Smith

  2. Department of Electrical Engineering, Signal and Image Processing Institute, Viterbi School of Engineering, University of Southern California, Los Angeles, 90089, California, USA

    Sangtae Ahn & Richard M Leahy

  3. Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, 90095, California, USA

    Tongtong Wu

  4. Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK

    Christine J Farr

  5. Department of Microbiology, Department of Medicine, and Department of Human Genetics, Immunology and Molecular Genetics, University of California, Los Angeles, 90095, California, USA

    Aldons J Lusis

  6. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, 90095, California, USA

    Kenneth Lange

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Contributions

C.C.P., A.S., A.H.K. and C.J.F. carried out the experiments; S.A., J.S.B., A.L., R.T.W. and T.W. did the statistical and computational analysis; C.C.P., A.J.L., R.M.L., K.L. and D.J.S. wrote the paper; D.J.S. devised the study.

Corresponding author

Correspondence to Desmond J Smith.

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Supplementary Methods, Supplementary Table 1, Supplementary Figures 1–6 (PDF 3215 kb)

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Park, C., Ahn, S., Bloom, J. et al. Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids. Nat Genet 40, 421–429 (2008). https://doi.org/10.1038/ng.113

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