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Fine mapping of regulatory loci for mammalian gene expression using radiation hybrids
Authors:Park Christopher C  Ahn Sangtae  Bloom Joshua S  Lin Andy  Wang Richard T  Wu Tongtong  Sekar Aswin  Khan Arshad H  Farr Christine J  Lusis Aldons J  Leahy Richard M  Lange Kenneth  Smith Desmond J
Institution:Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
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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