Article abstract
Nature Genetics 40, 421 - 429 (2008)
Published online: 23 March 2008 | Corrected online: 28 April 2008 | doi:10.1038/ng.113
There is an Erratum (May 2008) associated with this Article.
Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids
Christopher C Park1, Sangtae Ahn2, Joshua S Bloom1,7, Andy Lin1, Richard T Wang1, Tongtong Wu3,7, Aswin Sekar1, Arshad H Khan1, Christine J Farr4, Aldons J Lusis5, Richard M Leahy2, Kenneth Lange6 & Desmond J Smith1
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.
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
- Department of Electrical Engineering, Signal and Image Processing Institute, Viterbi School of Engineering, University of Southern California, Los Angeles, California 90089, USA.
- University of California Los Angeles School of Public Health, Department of Biostatistics, Los Angeles, California 90095, USA.
- Department of Genetics, University of Cambridge, Downing Street, Cambridge, CB2 3EH, UK.
- Department of Microbiology, Immunology and Molecular Genetics, Department of Medicine, and Department of Human Genetics, University of California, Los Angeles, California 90095, USA.
- Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
- 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.).
Correspondence to: Desmond J Smith1 e-mail: DSmith@mednet.ucla.edu