Treating messenger RNA transcript abundances as quantitative traits and mapping gene expression quantitative trait loci for these traits has been pursued in gene-specific ways. Transcript abundances often serve as a surrogate for classical quantitative traits in that the levels of expression are significantly correlated with the classical traits across members of a segregating population. The correlation structure between transcript abundances and classical traits has been used to identify susceptibility loci for complex diseases such as diabetes1 and allergic asthma2. One study recently completed the first comprehensive dissection of transcriptional regulation in budding yeast3, giving a detailed glimpse of a genome-wide survey of the genetics of gene expression. Unlike classical quantitative traits, which often represent gross clinical measurements that may be far removed from the biological processes giving rise to them, the genetic linkages associated with transcript abundance affords a closer look at cellular biochemical processes. Here we describe comprehensive genetic screens of mouse, plant and human transcriptomes by considering gene expression values as quantitative traits. We identify a gene expression pattern strongly associated with obesity in a murine cross, and observe two distinct obesity subtypes. Furthermore, we find that these obesity subtypes are under the control of different loci.
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Eaves, I. A. et al. Combining mouse congenic strains and microarray gene expression analyses to study a complex trait: the NOD model of type 1 diabetes. Genome Res. 12, 232–243 (2002)
Karp, C. L. et al. Identification of complement factor 5 as a susceptibility locus for experimental allergic asthma. Nature Immunol. 1, 221–226 (2000)
Brem, R. B., Yvert, G., Clinton, R. & Kruglyak, L. Genetic dissection of transcriptional regulation in budding yeast. Science 296, 752–755 (2002)
Claudio, L., Lee, T., Wolff, M. S. & Wetmur, J. G. A murine model of genetic susceptibility to lead bioaccumulation. Fundam. Appl. Toxicol. 35, 84–90 (1997)
Huang, Y. H., Chen, Y. T., Lai, J. J., Yang, S. T. & Yang, U. C. PALS db: Putative Alternative Splicing database. Nucleic Acids Res. 30, 186–190 (2002)
Yan, L., Otterness, D. M., Kozak, C. A. & Weinshilboum, R. M. Mouse nicotinamide N-methyltransferase gene: molecular cloning, structural characterization, and chromosomal localization. DNA Cell Biol. 17, 659–667 (1998)
Hughes, T. R. et al. Expression profiling using microarrays fabricated by an ink-jet oligonucleotide synthesizer. Nature Biotechnol. 19, 342–347 (2001)
Drake, T. A. et al. Genetic loci determining bone density in mice with diet-induced atherosclerosis. Physiol. Genomics 5, 205–215 (2001)
Timm, D. E., Baker, L. J., Mueller, H., Zidek, L. & Novotny, M. V. Structural basis of pheromone binding to mouse major urinary protein (MUP-I). Protein Sci. 10, 997–1004 (2001)
Metcalf, D. et al. Gigantism in mice lacking suppressor of cytokine signalling-2. Nature 405, 1069–1073 (2000)
Swift, L. L., Valyi-Nagy, K., Rowland, C. & Harris, C. Assembly of very low density lipoproteins in mouse liver: evidence of heterogeneity of particle density in the Golgi apparatus. J. Lipid Res. 42, 218–224 (2001)
Borecki, I. G., Rice, T., Perusse, L., Bouchard, C. & Rao, D. C. An exploratory investigation of genetic linkage with body composition and fatness phenotypes: the Quebec Family Study. Obesity Res. 2, 213–219 (1994)
Lembertas, A. V. et al. Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. J. Clin. Invest. 100, 1240–1247 (1997)
Damerval, C., Maurice, A., Josse, J. M. & de Vienne, D. Quantitative trait loci underlying gene product variation: a novel perspective for analyzing regulation of genome expression. Genetics 137, 289–301 (1994)
Causse, M. et al. Genetic dissection of the relationship between carbon metabolism and early growth in maize, with emphasis on key-enzyme loci. Mol. Breed. 1, 259–272 (1995)
Byrne, P. F. et al. Quantitative trait loci and metabolic pathways: genetic control of the concentration of maysin, a corn earworm resistance factor, in maize silks. Proc. Natl Acad. Sci. USA 93, 8820–8825 (1996)
Dausset, J. et al. Centre d'Etude du Polymorphisme Humain (CEPH): collaborative genetic mapping of the human genome. Genomics 6, 575–577 (1990)
van't Veer, L. J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530–536 (2002)
Tosatio, G. Generation of Epstein-Barr Virus (EBV)-immortalized B cell lines. Curr. Protoc. Immunol. 1, 7.22.1–7.22.3 (1991)
Troyer, A. F. Background of US hybrid corn. Crop Sci. 39, 601–626 (1999)
Hughes, T. R. et al. Functional discovery via a compendium of expression profiles. Cell 102, 109–126 (2000)
Amos, C. I. Robust variance-components approach for assessing genetic linkage in pedigrees. Am. J. Hum. Genet. 54, 535–543 (1994)
Lincoln, S. E., Daly, M. J. & Lander, E. S. MAPMAKER/QTL User's Manual (Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, 1993)
Basten, C. A., Weir, B. S. & Zeng, Z. B. QTL Cartographer User's Manual (Department of Statistics, North Carolina State University, Raleigh, 1999)
Fisch, R. D., Ragot, M. & Gay, G. A generalization of the mixture model in the mapping of quantitative trait loci for progeny from a biparental cross of inbred lines. Genetics 143, 571–577 (1996)
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Schadt, E., Monks, S., Drake, T. et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 422, 297–302 (2003). https://doi.org/10.1038/nature01434
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