Project description: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.
Project description:We have mapped regulatory loci for nearly all protein coding genes in the mammalian genome using microarray measurements from a panel of mouse/hamster radiation hybrids. Proof of principle transfection experiment. Pcdh7 (a gene identified as being a regulator of many genes) is transfected into A23 and HEK cells and compared to A23 and HEK cells transfected with an empty vector. Upregulated genes predicted by our approach are compared with the transfection experiments Keywords: tranfection, regulation of gene expression
Project description:We have mapped regulatory loci for nearly all protein coding genes in the mammalian genome using microarray measurements from a panel of mouse/hamster radiation hybrids. Keywords: regulation of gene expression
Project description:We have mapped regulatory loci for nearly all protein coding genes in the mammalian genome using microarray measurements from a panel of mouse/hamster radiation hybrids. Keywords: regulation of gene expression
Project description:We have mapped regulatory loci for nearly all protein coding genes in the mammalian genome using microarray measurements from a panel of mouse/hamster radiation hybrids. Keywords: regulation of gene expression
Project description:We have mapped regulatory loci for nearly all protein coding genes in the mammalian genome using microarray measurements from a panel of mouse/hamster radiation hybrids. Keywords: regulation of gene expression
Project description:Meiotic mapping of quantitative trait loci regulating expression (eQTLs) has allowed the construction of gene networks. However, the limited mapping resolution of these studies has meant that genotype data are largely ignored, leading to undirected networks that fail to capture regulatory hierarchies. Here we use high resolution mapping of copy number eQTLs (ceQTLs) in a mouse-hamster radiation hybrid (RH) panel to construct directed genetic networks in the mammalian cell. The RH network covering 20,145 mouse genes had significant overlap with, and similar topological structures to, existing biological networks. Upregulated edges in the RH network had significantly more overlap than downregulated. This suggests repressive relationships between genes are missed by existing approaches, perhaps because the corresponding proteins are not present in the cell at the same time and therefore unlikely to interact. Gene essentiality was positively correlated with connectivity and betweenness centrality in the RH network, strengthening the centrality-lethality principle in mammals. Consistent with their regulatory role, transcription factors had significantly more outgoing edges (regulating) than incoming (regulated) in the RH network, a feature hidden by conventional undirected networks. Directed RH genetic networks thus showed concordance with pre-existing networks while also yielding information inaccessible to current undirected approaches.