Journal ArticleDOI
Genetics of gene expression surveyed in maize, mouse and man
Eric E. Schadt,Stephanie A. Monks,Thomas A. Drake,Aldons J. Lusis,Nam Che,Veronica Colinayo,Thomas G. Ruff,Stephen B. Milligan,John Lamb,Guy Cavet,Peter S. Linsley,Mao Mao,Roland Stoughton,Stephen H. Friend +13 more
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TLDR
In this paper, the authors describe comprehensive genetic screens of mouse, plant and human transcriptomes by considering gene expression values as quantitative traits and identify a gene expression pattern strongly associated with obesity in a murine cross and observe two distinct obesity subtypes.Abstract:
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 diabetes and allergic asthma. One study recently completed the first comprehensive dissection of transcriptional regulation in budding yeast, 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.read more
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The sva package for removing batch effects and other unwanted variation in high-throughput experiments
TL;DR: The sva package is described, which supports surrogate variable estimation with the sva function, direct adjustment for known batch effects with the ComBat function and adjustment for batch and latent variables in prediction problems with the fsva function.
Journal ArticleDOI
Capturing heterogeneity in gene expression studies by surrogate variable analysis.
Jeffrey T. Leek,John D. Storey +1 more
TL;DR: This work introduces “surrogate variable analysis” (SVA) to overcome the problems caused by heterogeneity in expression studies and shows that SVA increases the biological accuracy and reproducibility of analyses in genome-wide expression studies.
Journal ArticleDOI
Relative Impact of Nucleotide and Copy Number Variation on Gene Expression Phenotypes
Barbara E. Stranger,Matthew S. Forrest,Mark J Dunning,Catherine E. Ingle,Claude Beazley,Natalie P. Thorne,Richard Redon,Christine P. Bird,Anna De Grassi,Charles Lee,Charles Lee,Chris Tyler-Smith,Nigel P. Carter,Stephen W. Scherer,Stephen W. Scherer,Simon Tavaré,Simon Tavaré,Panagiotis Deloukas,Matthew E. Hurles,Emmanouil T. Dermitzakis +19 more
TL;DR: To determine the overall contribution of CNVs to complex phenotypes, association analyses of expression levels with SNPs and CNVs in individuals who are part of the International HapMap project show little overlap between the two types of variation.
Journal ArticleDOI
Heritability in the genomics era — concepts and misconceptions
TL;DR: This work has shown that despite continuous misunderstandings and controversies over its use and application, heritability remains key to the response to selection in evolutionary biology and agriculture, and to the prediction of disease risk in medicine.
Journal ArticleDOI
Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma
Miriam F. Moffatt,Michael Kabesch,Liming Liang,Anna L. Dixon,David P. Strachan,Simon Heath,Martin Depner,Andrea von Berg,Albrecht Bufe,Ernst Rietschel,Andrea Heinzmann,Burkard Simma,Thomas Frischer,Saffron A.G. Willis-Owen,Kenny C. C. Wong,Thomas Illig,Christian Vogelberg,Stephan K. Weiland,Erika von Mutius,Gonçalo R. Abecasis,Martin Farrall,Ivo Gut,G. Mark Lathrop,William O.C.M. Cookson +23 more
TL;DR: The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.
References
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Gene expression profiling predicts clinical outcome of breast cancer
Laura J. van't Veer,Hongyue Dai,Marc J. van de Vijver,Yudong D. He,Augustinus A. M. Hart,Mao Mao,Hans Peterse,Karin van der Kooy,Matthew J. Marton,Anke T. Witteveen,George J. Schreiber,Ron M. Kerkhoven,Christopher J. Roberts,Peter S. Linsley,René Bernards,Stephen H. Friend +15 more
TL;DR: DNA microarray analysis on primary breast tumours of 117 young patients is used and supervised classification is applied to identify a gene expression signature strongly predictive of a short interval to distant metastases (‘poor prognosis’ signature) in patients without tumour cells in local lymph nodes at diagnosis, providing a strategy to select patients who would benefit from adjuvant therapy.
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Nature and composition of the continental crust: A lower crustal perspective
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Journal ArticleDOI
Functional Discovery via a Compendium of Expression Profiles
Timothy P. Hughes,Matthew J. Marton,Allan R. Jones,Christopher J. Roberts,Roland Stoughton,Christopher D. Armour,Holly A. Bennett,Ernest M. Coffey,Hongyue Dai,Yudong D. He,Matthew J. Kidd,Amy M King,Michael R. Meyer,David J. Slade,Pek Yee Lum,Sergey B. Stepaniants,Daniel D. Shoemaker,Daniel J Gachotte,Kalpana Chakraburtty,Julian A. Simon,Martin Bard,Stephen H. Friend +21 more
TL;DR: A reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae is constructed, and it is shown that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles.
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Composition of the Earth
TL;DR: In this article, the authors reported that the resulting densities in the lower mantle are in good agreement with shock-wave measurements on rocks having FeO contents in the range 10 ± 2% by weight.
Journal ArticleDOI
Mantle geochemistry: the message from oceanic volcanism
TL;DR: Basaltic volcanism'samples' the Earth's mantle to great depths, because solid-state convection transports deep material into the (shallow) melting region as mentioned in this paper.