Genetics of global gene expression
Abstract
A new field of genetic analysis of global gene expression has emerged in recent years, driven by the realization that traditional techniques of linkage and association analysis can be applied to thousands of transcript levels measured by microarrays. Genetic dissection of transcript abundance has shed light on the architecture of quantitative traits, provided a new approach for connecting DNA sequence variation with phenotypic variation, and improved our understanding of transcriptional regulation and regulatory variation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous eQTL studies in genetically diverse populations suggest that the most significant eQTL tend to be local.
“Previous eQTL studies in genetically diverse populations suggest that the most significant eQTL tend to be local (Rockman and Kruglyak 2006; Pickrell et al. 2010; Aylor et al. 2011; Lappalainen et al. 2013).”
From RNA-Seq Alignment to Individualized Genomes Improves Transcript Abundance Estimates in Multiparent Populations (2014) · cites this paper as Rockman and Kruglyak 2006
Cites
An integrative genomics approach to infer causal associations between gene expression and disease
Schadt, E. E., Lamb, J., Yang, X., Zhu, J., Edwards, S., GuhaThakurta, D., Sieberts, S. K., Monks, S., Reitman, M., Zhang, C., et al. (2005) · Nature Genetics · doi:10.1038/ng1589 · Cited by 1,043 · see citing works
Variation in gene expression within and among natural populations
Oleksiak, M. F., Churchill, G. A., & Crawford, D. L. (2002) · Nature Genetics · doi:10.1038/ng983 · Cited by 736 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Heritability in the genomics era — concepts and misconceptions
Visscher, P. M., Hill, W. G., & Wray, N. R. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2322 · Cited by 1,921 · see citing works
Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags
Hohenlohe, P. A., Bassham, S., Etter, P. D., Stiffler, N., Johnson, E. A., & Cresko, W. A. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000862 · Cited by 1,390 · see citing works
“analyses [42–47].”
Understanding mechanisms underlying human gene expression variation with RNA sequencing
Pickrell, J. K., Marioni, J. C., Pai, A. A., Degner, J. F., Engelhardt, B. E., Nkadori, E., Veyrieras, J.-B., Stephens, M., Gilad, Y., & Pritchard, J. K. (2010) · Nature · doi:10.1038/nature08872 · Cited by 1,256 · see citing works
The genetics of quantitative traits: challenges and prospects
Mackay, T. F. C., Stone, E. A., & Ayroles, J. F. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2612 · Cited by 1,292 · see citing works
“Intermediate molecular phenotypes such as transcript abundance also vary genetically in populations and are themselves quantitative trait”
BackgroundTuning gene expression to changing environments: from rapid responses to evolutionary adaptation
López-Maury, L., Marguerat, S., & Bähler, J. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2398 · Cited by 1,061 · see citing works
Stegle, O., Parts, L., Piipari, M., Winn, J., & Durbin, R. (2012) · Nature Protocols · doi:10.1038/nprot.2011.457 · Cited by 1,049 · see citing works
“Oliver Stegle 1,2,6 , Leopold Parts Max Planck Institute for Intelligent Systems, Tübingen, Germany.”
BackgroundThe role of regulatory variation in complex traits and disease
Albert, F. W., & Kruglyak, L. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3891 · Cited by 1,047 · see citing works
Self-citationMarker-Assisted Selection in Plant Breeding: From Publications to Practice
Xu, Y.-B., & Crouch, J. (2008) · Crop Science · doi:10.2135/cropsci2007.04.0191 · Cited by 927 · see citing works
“Dissecting the architecture of quantitative traits in this way connects DNA sequence variation with phenotypic variation, and is improving our understanding of transcriptional regulation and regulatory variation (Rockman and Kruglyak, 2006).”
BackgroundEvolution, the Extended Synthesis
Pigliucci, M., & Müller, G. (2010) · The MIT Press eBooks · doi:10.7551/mitpress/9780262513678.001.0001 · Cited by 966 · see citing works
Mapping complex disease traits with global gene expression
Cookson, W., Liang, L., Abecasis, G., Moffatt, M., & Lathrop, M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2537 · Cited by 849 · see citing works
THE QTN PROGRAM AND THE ALLELES THAT MATTER FOR EVOLUTION: ALL THAT'S GOLD DOES NOT GLITTER
Rockman, M. V. (2011) · Evolution · doi:10.1111/j.1558-5646.2011.01486.x · Cited by 661 · see citing works
“For Fisher, the sphere was typically quite small, as populations would adapt by continuous pursuit of a receding optimum, which, like a carrot on a stick, draws the population forward but remains forever just out of reach (Fisher 1930; Frank and Slatkin 1992).”
BackgroundSelf-citationEvolutionary Genetics of Genome Merger and Doubling in Plants
Doyle, J. J., Flagel, L., Paterson, A. H., Rapp, R. A., Soltis, P. S., Soltis, P. S., & Wendel, J. F. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.42.110807.091524 · Cited by 680 · see citing works
“Gene expression is context dependent (90), and alleles from the diploid progenitor(s) will experience a novel context in the polyploid.”
BackgroundVariation in Transcription Factor Binding Among Humans
Kasowski, M. M., Grubert, F., Heffelfinger, C., Hariharan, M., Asabere, A., Waszak, S., Habegger, L., Rozowsky, J., Shi, M.-Y., Urban, A., et al. (2010) · Science · doi:10.1126/science.1183621 · Cited by 625 · see citing works
Advantages and limitations of current network inference methods
Smet, R. D., & Marchal, K. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2419 · Cited by 510 · see citing works
Hormone signalling crosstalk in plant growth regulation.
Depuydt, S., & Hardtke, C. (2011) · Current Biology · doi:10.1016/j.cub.2011.03.013 · Cited by 523 · see citing works
Principles for the post-GWAS functional characterization of cancer risk loci
Freedman, M. L., Monteiro, Á. N. A., Gayther, S. A., Coetzee, G. A., Risch, A., Plass, C., Casey, G., Biasi, M. D., Carlson, C., Duggan, D. J., et al. (2011) · Nature Genetics · doi:10.1038/ng.840 · Cited by 436 · see citing works
“The terminology of local and distant in this context is preferred to cis and trans , which connote mechanis”
BackgroundRind, A., & Isenberg, D. (2021) · Reference Module in Biomedical Sciences · doi:10.1016/b978-0-12-820472-6.00070-0 · Cited by 479
“Cell and context specificity of regulatory variation Genetic variations regulate gene expression levels spatially and temporally, thus leading to the differentiation and maintenance of highly specialised cell and tissue types that underlie phenotypic differences across individuals [79].”
Gene–Environment Interaction in Yeast Gene Expression
Smith, E. N., & Kruglyak, L. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060083 · Cited by 421 · see citing works
“Recently, gene transcript abundance has been used as a model to study the genetics of thousands of quantitative traits at a time [7,8].”
MethodSelf-citationRegulatory divergence in <i>Drosophila</i> revealed by mRNA-seq
McManus, C. J., Coolon, J. D., Duff, M. O., Eipper-Mains, J., Graveley, B. R., & Wittkopp, P. J. (2010) · Genome Research · doi:10.1101/gr.102491.109 · Cited by 381 · see citing works
“…the same species (Schadt et al. 2003) and 35% of genes for individuals from different species (Hsieh et al. 2003; for more complete reviews of expression differences within and between species, see Gibson and Weir 2005; Ranz and Machado 2006; Rockman and Kruglyak 2006; Whitehead and Crawford 2006).”
BackgroundGenetic basis of proteome variation in yeast
Foss, E. J., Radulovic, D., Shaffer, S. A., Ruderfer, D. M., Bedalov, A., Goodlett, D. R., & Kruglyak, L. (2007) · Nature Genetics · doi:10.1038/ng.2007.22 · Cited by 358 · see citing works
“22" language="eng" relation="no"> A number of recent studies have shown that transcript levels vary among individuals of a species, and that genetic linkage analysis can be used to identify quantitative trait loci that influence the transcript levels of individual genes and groups of gene”
BackgroundSelf-citationKeurentjes, J., Fu, J.-Y., Terpstra, I., García, J. M., van den Ackerveken, G., Snoek, L. B., Peeters, A., Vreugdenhil, D., Koornneef, M., & Jansen, R. (2007) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0610429104 · Cited by 366 · see citing works
Defining the consequences of genetic variation on a proteome-wide scale
Chick, J. M., Munger, S. C., Simecek, P., Huttlin, E. L., Choi, K., Gatti, D. M., Raghupathy, N., Svenson, K. L., Churchill, G. A., & Gygi, S. P. (2016) · Nature · doi:10.1038/nature18270 · Cited by 361 · see citing works
Immune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336 · see citing works
“Researchers have used GWASs and genotyping results combined with gene expression data to perform an analysis of expression quantitative trait loci (eQTLs), to determine whether a single nucleotide polymorphism (SNP) from a GWAS is associated with altered expression of either local (cis-eQTL) or distant (trans-eQTL) ge…”
MethodThe evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype.
Cowen, L. E. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1835 · Cited by 311 · see citing works
Effect of natural genetic variation on enhancer selection and function
Heinz, S., Romanoski, C. E., Benner, C., Allison, K. A., Kaikkonen, M. U., Orozco, L. D., & Glass, C. K. (2013) · Nature · doi:10.1038/nature12615 · Cited by 298 · see citing works
Systematic Mapping of Genetic Interaction Networks
Dixon, S. J., Costanzo, M., Baryshnikova, A., Andrews, B., & Boone, C. M. (2008) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.073003.114751 · Cited by 290 · see citing works
“single F2 cross between parents of different but compatible genetic backgrounds as reagents to map genetic interactions (15, 17, 42, 106).”
Learning from Co-expression Networks: Possibilities and Challenges
Serin, E. A. R., Nijveen, H., Hilhorst, H., & Ligterink, W. (2016) · Frontiers in Plant Science · doi:10.3389/fpls.2016.00444 · Cited by 272 · see citing works
“…depending on whether they co-localize with the physical position of the studied gene or are located elsewhere in the genome, respectively (Rockman and Kruglyak, 2006). eQTLs can also be classified as cis- or trans-acting based on the location of the associated causal polymorphism in the gene…”
BackgroundThe environmental contribution to gene expression profiles
Gibson, G. (2008) · Nature reviews genetics · doi:10.1038/nrg2383 · Cited by 269 · see citing works
“The potential of expression profiling to lead us to the genes and genetic pathways that are involved in a wide range of complex traits is further demonstrated by the application of genetical genomics”
BackgroundMethods for biological data integration: perspectives and challenges
Gligorijević, V., & Pržulj, N. (2015) · Journal of The Royal Society Interface · doi:10.1098/rsif.2015.0571 · Cited by 274 · see citing works
Reverse engineering the genotype–phenotype map with natural genetic variation
Rockman, M. V. (2008) · Nature · doi:10.1038/nature07633 · Cited by 231 · see citing works
“The use of natural genetic variation to probe the causal network that links genotype and phenotype has grown recently as large data sets have been generated for many experimental model species, crops and human”
BackgroundSelf-citationGenetics of human gene expression: mapping DNA variants that influence gene expression
Cheung, V. G., & Spielman, R. S. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2630 · Cited by 233 · see citing works
Molecular and evolutionary processes generating variation in gene expression
Hill, M. S., Zande, P. V., & Wittkopp, P. J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-00304-w · Cited by 262 · see citing works
Serre, D., Gurd, S., Ge, B., SLADEK, R. M., Sinnett, D., Harmsen, E., Bibikova, M. V., Chudin, E., Barker, D. L. A., Dickinson, T. A., et al. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000006 · Cited by 224 · see citing works
“In this context, it is noteworthy that total gene expression mapping has been much more successful in mice and yeast for which the genetic heterogeneity is much lower and can be controlled (reviewed in [9,10,51]).”
BackgroundSystems biology in cardiovascular disease: a multiomics approach
Joshi, A., Rienks, M., Theofilatos, K., & Mayr, M. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00477-1 · Cited by 305 · see citing works
Epigenome dynamics: a quantitative genetics perspective
Johannes, F., Colot, V., & Jansen, R. (2008) · Nature reviews genetics · doi:10.1038/nrg2467 · Cited by 230 · see citing works
Functional Genetic Variants Revealed by Massively Parallel Precise Genome Editing
Sharon, E., Chen, S.-A. A., Khosla, N. M., Smith, J. D., Pritchard, J. K., & Fraser, H. B. (2018) · Cell · doi:10.1016/j.cell.2018.08.057 · Cited by 225 · see citing works
“Traditionally, the phenotypic effects of natural genetic variation have been studied via quantitative trait locus (QTL) mapping (Mackay et al., 2009; Pickrell et al., 2010; Rockman and Kruglyak, 2006).”
BackgroundGenetic analysis of radiation-induced changes in human gene expression
Smirnov, D., Morley, M., Shin, E., Spielman, R., & Cheung, V. (2009) · Nature · doi:10.1038/nature07940 · Cited by 221 · see citing works
Ribosome profiling reveals post-transcriptional buffering of divergent gene expression in yeast
McManus, C. J., May, G. E., Spealman, P., & Shteyman, A. (2014) · Genome Research · doi:10.1101/gr.164996.113 · Cited by 219 · see citing works
“Consequently, evolution of gene regulation has been suggested as a major source of phenotypic diversity (Carroll 2005; Rockman and Kruglyak 2006).”
Zayed, A., & Robinson, G. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155517 · Cited by 206 · see citing works
“Studies of several model genetic organisms have demonstrated a great deal of heritability in patterns of gene expression (34, 37, 42, 93, 101).”
BackgroundSkelly, D. A., Johansson, M., Madeoy, J., Wakefield, J., & Akey, J. M. (2011) · Genome Research · doi:10.1101/gr.119784.110 · Cited by 203 · see citing works
Bloom, J. S., Khan, Z., Kruglyak, L., Singh, M., & Caudy, A. A. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-221 · Cited by 178 · see citing works
“Local linkages can be mechanistically explained by polymorphisms in promoters, 3' untranslated regions, or coding sequence [15].”
BackgroundSelf-citationWhat would you do if you could sequence everything?
Kahvejian, A., Quackenbush, J., & Thompson, J. F. (2008) · Nature Biotechnology · doi:10.1038/nbt1494 · Cited by 189 · see citing works
Transcript profiling in host-pathogen interactions.
Wise, R., Moscou, M., Bogdanove, A., & Whitham, S. (2007) · Annual Review of Phytopathology · doi:10.1146/annurev.phyto.45.011107.143944 · Cited by 185 · see citing works
“Key aspects of experimental design such as size of population, type of population [recombinant inbred lines (RILs), double haploids (DHs), back crosses (BCs)], measurement of quantitative traits, statistical models, and permutation testing have been extensively reviewed (34, 89, 113, 118).”
Ding, J., Gudjonsson, J. E., Liang, L., Stuart, P. E., Li, Y., Chen, W., Weichenthal, M., Ellinghaus, E., Franke, A., Cookson, W., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.10.024 · Cited by 180 · see citing works
Polymorphic Cis- and Trans-Regulation of Human Gene Expression
Cheung, V. G., Nayak, R. R., Wang, I. X., Elwyn, S., Cousins, S. M., Morley, M. P., & Spielman, R. S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000480 · Cited by 165 · see citing works
“To take into account the imprecision of linkage, we define regulatory regions that are within 5 Mb of the target genes as proximal and those that are greater than 5 Mb or on another chromosome as distal to the target genes [20].”
BackgroundNatural selection on cis and trans regulation in yeasts.Preprint
Emerson, J. J., Hsieh, L.-C., Sung, H.-M., Wang, T.-Y., Huang, C.-J., Lu, H. H.-S., Lu, M., Wu, S.-H., & Li, W.-H. (2010) · Genome Research · doi:10.1101/gr.101576.109 · Cited by 177 · see citing works
Andersen, E. C., Bloom, J. S., Gerke, J., & Kruglyak, L. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004156 · Cited by 154 · see citing works
“One promising approach to connect DNA sequence variation to phenotypic variation is analysis of gene expression QTL (eQTL) [33].”
BackgroundSelf-citationGenetic variation in MHC proteins is associated with T cell receptor expression biases
Sharon, E., Sibener, L., Battle, A., Fraser, H., Garcia, K., & Pritchard, J. (2016) · Nature Genetics · doi:10.1038/ng.3625 · Cited by 173 · see citing works
“Here, we address the question of how the host genotype influences the make-up of the TCR repertoire using expression quantitative trait loci (eQTL) analysis 28 of a large human cohort 29 for which both RNA sequencing of peripheral blood and genotyping data are available (Fig.”
Sim, S., Jupatanakul, N., Ramirez, J. L., Kang, S., Romero-Vivas, C. M., Mohammed, H. P., & Dimopoulos, G. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002295 · Cited by 157 · see citing works
“Furthermore, a mutation in a regulatory locus can change the expression of numerous target genes (reviewed in [14]).”
BackgroundComparative Analysis of Gene Regulatory Networks: From Network Reconstruction to Evolution
Thompson, D. A., Regev, A., & Roy, S. (2015) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100913-012908 · Cited by 170 · see citing works
“…by profiling of RNA levels; and (e) expression quantitative trait loci (eQTL) analyses, which can link genetic changes to their effects on gene expression in cis or in trans (Brem 2002, Fraser et al. 2011, Göring et al. 2007, Majewski & Pastinen 2011, Rockman & Kruglyak 2006, Stranger & Raj 2013).”
BackgroundDumas, M., Wilder, S. P., Bihoreau, M., Barton, R., Fearnside, J. F., Argoud, K., Damato, L., Wallis, R., Blancher, C., Keun, H., et al. (2007) · Nature Genetics · doi:10.1038/ng2026 · Cited by 153 · see citing works
Evolutionary Tinkering with Conserved Components of a Transcriptional Regulatory Network
Lavoie, H., Hogues, H., Mallick, J., Sellam, A., Nantel, A., & Whiteway, M. S. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000329 · Cited by 133 · see citing works
Towards the identification of the loci of adaptive evolution
Pardo‐Díaz, C., Salazar, C. A., & Jiggins, C. D. (2014) · Methods in Ecology and Evolution · doi:10.1111/2041-210x.12324 · Cited by 131 · see citing works
“WhenDNA variation associated with phenotypic change does not occur in protein-coding regions, examining the expression pattern of genes provides an important complementary method to test for regulatory change (Rockman & Kruglyak 2006; Hoekstra & Coyne 2007; Hofmann et al. 2009).”
MethodTaylor, D. L., Jackson, A., Narisu, N., Hemani, G., Erdos, M. R., Chines, P. S., Swift, A. J., Idol, J., Didion, J. P., Welch, R., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814263116 · Cited by 167 · see citing works
Detection and interpretation of expression quantitative trait loci (eQTL)
Michaelson, J. J., Loguercio, S., & Beyer, A. (2009) · Methods · doi:10.1016/j.ymeth.2009.03.004 · Cited by 131 · see citing works
eQED: an efficient method for interpreting eQTL associations using protein networks
Suthram, S., Beyer, A., Karp, R. M., Eldar, Y. C., & Ideker, T. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.4 · Cited by 128 · see citing works
“Two of the core challenges (Rockman and Kruglyak, 2006; Schadt and Lum, 2006) in understanding and explaining eQTL associations are (1) Fine mapping : Due to the spacing of genetic markers and/ or linkage disequilibrium, several genes can reside near each marker.”
BackgroundSequence Polymorphisms Cause Many False cis eQTLs
Alberts, R., Terpstra, P., Li, Y., Breitling, R., Nap, J., & Jansen, R. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000622 · Cited by 142 · see citing works
“is said to be a local eQTL if it is on or near the genomic position of the gene, or distant if it is located elsewhere [2].”
BackgroundGenetics of single-cell protein abundance variation in large yeast populations
Albert, F. W., Treusch, S., Shockley, A. H., Bloom, J. S., & Kruglyak, L. (2014) · Nature · doi:10.1038/nature12904 · Cited by 141 · see citing works
Self-citationEvolution at two levels of gene expression in yeast
Artieri, C. G., & Fraser, H. B. (2014) · Genome Research · doi:10.1101/gr.165522.113 · Cited by 138 · see citing works
“More recently, a major focus of modern evolutionary genetics has been to understand the molecular basis of regulatory variation within and between species (Carroll 2005; Rockman and Kruglyak 2006).”
BackgroundGenetic Architecture of Transcript-Level Variation in Humans
Duan, S., Huang, R. S., Zhang, W., Bleibel, W. K., Roe, C. A., Clark, T. A., Chen, T. X., Schweitzer, A. C., Blume, J. E., Cox, N. J., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.03.006 · Cited by 131 · see citing works
“Moreover, transcriptional-expression differences can be mapped to one or more segments of DNA close to or distant from the genomic location of the gene.(3) These segments of DNA, referred to as expression quantitative trait loci (eQTLs), or expression quantitative nucleotides (eQTNs) at the level of the individual pol…”
BackgroundGenome-wide gene expression regulation as a function of genotype and age in C. elegans.Preprint
Viñuela, A., Snoek, L. B., Riksen, J., & Kammenga, J. (2010) · Genome Research · doi:10.1101/gr.102160.109 · Cited by 136 · see citing works
“Genetic mapping of gene expression regulatory loci (eQTL) provides a means to address this problem (Jansen and Nap 2001; Rockman and Kruglyak 2006). eQTL can be cis- or trans-acting, reflecting local and distant regulation of gene expression, respec- tively.”
BackgroundThe molecularization of public sector crop breeding: progress, problems, and prospects
Dwivedi, S., Crouch, J., Mackill, D., Xu, Y.-B., Blair, M., Ragot, M., Upadhyaya, H., & Ortiz, R. (2007) · Advances in agronomy · doi:10.1016/s0065-2113(07)95003-8 · Cited by 136 · see citing works
Metabolomic prediction of yield in hybrid rice.
Xu, S.-Z., Xu, Y., Gong, L., & Zhang, Q.-F. (2016) · The Plant Journal · doi:10.1111/tpj.13242 · Cited by 135 · see citing works
“Previously, microarray data were analyzed largely in relation to 77 genomic data, called eQTL mapping (Bing and Hoeschele 2005, Keurentjes et al. 2007, 78 Rockman and Kruglyak 2006, Wang et al. 2014, West et al. 2007).”
MethodA Statistical Framework for eQTL Mapping Using RNA‐seq Data
Sun, W. (2011) · Biometrics · doi:10.1111/j.1541-0420.2011.01654.x · Cited by 117 · see citing works
“This trend was expected, because generally cis -eQTL affected the expression more directly than trans -eQTL, which often involved some other proteins (Rockman and Kruglyak, 2006), hence cis -eQTLs tended to have stronger effects.”
BackgroundMapping, Fine Mapping, and Molecular Dissection of Quantitative Trait Loci in Domestic Animals
Georges, M. (2007) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.8.080706.092408 · Cited by 132 · see citing works
“One possible explanation for a local eQTL is a cis-acting regulatory mutation that directly controls the transcript level of the corresponding gene, whereas a distant eQTL necessarily implies a trans-acting molecular mechanism (47, 82).”
BackgroundThe human Major Histocompatibility Complex as a paradigm in genomics research
Vandiedonck, C., & Knight, J. C. (2009) · Briefings in Functional Genomics and Proteomics · doi:10.1093/bfgp/elp010 · Cited by 120 · see citing works
Künstner, A., Wolf, J. B. W., Backström, N., Whitney, O., Balakrishnan, C. N., Day, L. B., Edwards, S. V., Janes, D. E., Schlinger, B. A., Wilson, R. K., et al. (2010) · Molecular Ecology · doi:10.1111/j.1365-294x.2009.04487.x · Cited by 108 · see citing works
“…a few examples, gene expression (transcriptome) profiling has helped to reveal how variation in gene regulation can be tied to phenotypic variation (Rockman & Kruglyak 2006), the use of genome-wide sets of genetic markers have greatly facilitated mapping of trait loci in pedigrees (linkage…”
The effects of genetic variation on gene expression dynamics during development
Francesconi, M., & Lehner, B. (2013) · Nature · doi:10.1038/nature12772 · Cited by 126 · see citing works
Integrated study of copy number states and genotype calls using high-density SNP arrays
Sun, W., Wright, F., Tang, Z., Nordgard, S. H., van Loo, P., Yu, T.-W., Kristensen, V., & Perou, C. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp493 · Cited by 125 · see citing works
“For example, gene expression quantitative trait loci studies have attracted many research interests recently (41).”
BackgroundPromoter architecture and the evolvability of gene expression
Tirosh, I., Barkai, N., & Verstrepen, K. J. (2009) · Journal of Biology · doi:10.1186/jbiol204 · Cited by 108 · see citing works
“Two approaches have been used to distinguish the effects of cis and trans mutations on gene expression on a genomic scale: genetical genomics [51,53] and analysis of hybrid species [15,54].”
MethodRenaut, S., Nolte, A., & Bernatchez, L. (2009) · Molecular biology and evolution · doi:10.1093/molbev/msp017 · Cited by 121 · see citing works
Schröder, A., Klein, K., Winter, S., Schwab, M. G., Bonin, M., Zell, A., & Zanger, U. M. (2011) · The Pharmacogenomics Journal · doi:10.1038/tpj.2011.44 · Cited by 104 · see citing works
The influence of genetic variation on gene expressionPreprint
Williams, R. B. H., Chan, E. K. F., Cowley, M. J., & Little, P. (2007) · Genome Research · doi:10.1101/gr.6981507 · Cited by 114 · see citing works
“We draw attention to recent reviews from Rockman and Kruglyak (2006) and Gibson and Weir (2005), as well as a special issue of Mammalian Genome (June 2006), which contains several review articles on more specialized aspects of this field.”
BackgroundKeurentjes, J. J. B., Ronan Sulpice, A., Gibon, Y., Steinhauser, M.-C., Fu, J., Koornneef, M., Stitt, M., & Vreugdenhil, D. (2008) · Genome biology · doi:10.1186/gb-2008-9-8-r129 · Cited by 118 · see citing works
“Locally observed eQTLs indicate that regulation occurs in cis, whereas distant eQTLs suggests regulation to occur in trans [44].”
Systems genetics analysis of gene-by-environment interactions in human cells
Romanoski, C. E., Lee, S., Kim, M. J., Ingram-Drake, L., Plaisier, C. L., Yordanova, R., Tilford, C., Guan, B., He, A., Gargalovic, P. S., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.02.002 · Cited by 111 · see citing works
Contrasting Frequencies and Effects ofcis- andtrans-Regulatory Mutations Affecting Gene Expression
Metzger, B. P. H., Duveau, F., Yuan, D. C., Tryban, S., Yang, B., & Wittkopp, P. J. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw011 · Cited by 109 · see citing works
“In particular, identification of the specific genetic loci responsible for variation in gene expression has revealed differences in both the relative frequency and average effects of cis - and trans -acting loci (Gibson and Weir 2005; Rockman and Kruglyak 2006; Gilad et al. 2008).”
BackgroundInfluentialGenetic Variation Shapes Protein Networks Mainly through Non-transcriptional Mechanisms
Foss, E. J., Radulovic, D., Shaffer, S. A., Goodlett, D. R., Kruglyak, L., & Bedalov, A. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001144 · Cited by 103 · see citing works
“Consistent with numerous reports in both this collection of yeast strains and other populations [32–34], we find that at the transcript level, cis regulation of the 354 genes in this study is relatively common (Figure 5): at 1% FDR, we map regulators of 170 transcripts, 22 of which act in cis.”
ResultSelf-citationThe genomic determinants of genotype × environment interactions in gene expression.
Grishkevich, V., & Yanai, I. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.05.006 · Cited by 107 · see citing works
Genetic architecture of regulatory variation in Arabidopsis thaliana.Preprint
Zhang, X., Cal, A. J., & Borevitz, J. (2011) · Genome Research · doi:10.1101/gr.115337.110 · Cited by 104 · see citing works
“Transacting polymorphisms are located elsewhere in the genome and affect the transcript abundance of both alleles of the target gene (Rockman and Kruglyak 2006).”
Expression Quantitative Trait Loci Are Highly Sensitive to Cellular Differentiation State
Gerrits, A., Li, Y., Tesson, B. M., Bystrykh, L. V., Weersing, E., Ausema, A., Dontje, B., Wang, X., Breitling, R., Jansen, R. C., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000692 · Cited by 91 · see citing works
“, those that map near (less than 10 Mb from) the gene which encodes the transcript (local) and those that map elsewhere in the genome (distant) [15].”
Expression Quantitative Trait Loci: Replication, Tissue- and Sex-Specificity in Mice
van Nas, A., Ingram-Drake, L. A., Sinsheimer, J. S., Wang, S. S., Schadt, E. E., Drake, T. A., & Lusis, A. J. (2010) · Genetics · doi:10.1534/genetics.110.116087 · Cited by 96 · see citing works
“…of gene expression provides a useful form of functional variation for positional cloning and can facilitate the modeling of causal interactions and biologic networks (Schadt et al. 2005; Ghazalpour et al. 2006; Rockman and Kruglyak 2006; Cookson et al. 2009; Montgomery and Dermitzakis 2009).”
BackgroundExpression Quantitative Trait Loci Mapping With Multivariate Sparse Partial Least Squares Regression
Chun, H., & Keleş, S. (2009) · Genetics · doi:10.1534/genetics.109.100362 · Cited by 97 · see citing works
“The minimization problem in (2), with an updated M in step 2.1, can allow a set of variables to be admitted to the active set A simultaneously in step 2.2.”
BackgroundInfluentialA sex-linked supergene controls sperm morphology and swimming speed in a songbird
Kim, K.-W., Bennison, C., Hemmings, N., Brookes, L. M., Hurley, L., Griffith, S., Burke, T., Birkhead, T., & Slate, J. (2017) · Nature Ecology & Evolution · doi:10.1038/s41559-017-0235-2 · Cited by 96 · see citing works
Genomic Networks of Hybrid Sterility
Turner, L., White, M. A., Tautz, D., & Payseur, B. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004162 · Cited by 96 · see citing works
“These proximal eQTL are likely to be cis regulatory elements [33,35].”
BackgroundSchaefke, B., Emerson, J. J., Wang, T.-Y., Lu, M., Hsieh, L.-C., & Li, W.-H. (2013) · Molecular biology and evolution · doi:10.1093/molbev/mst114 · Cited by 93 · see citing works
“…reliably distinguish between cis- and trans-acting elements, as a trans regulator also can be located on the same chromosome in close proximity to the target gene, and a cis regulatory element (e.g., an enhancer) can be distantly located from it (Rockman and Kruglyak 2006; Emerson and Li 2010).”
BackgroundGruber, J. D., Vogel, K. R., Kalay, G., & Wittkopp, P. J. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002497 · Cited by 87 · see citing works
“The relative contribution of cis- and trans-acting mutations to polymorphic and divergent gene expression has also been examined in a variety of species, either using genetic mapping or allele-specific expression to infer changes in cis- and trans-regulation (reviewed by [14,54–56]).”
BackgroundGresham, D., Boer, V., Caudy, A., Ziv, N., Brandt, N., Storey, J., & Botstein, D. (2011) · Genetics · doi:10.1534/genetics.110.120766 · Cited by 89
Matoba, N., Liang, D., Sun, H., Aygün, N., McAfee, J. C., Davis, J. E., Raffield, L. M., Qian, H., Piven, J., Li, Y., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00953-9 · Cited by 95 · see citing works
Neavin, D. R., Nguyen, Q. H., Daniszewski, M., Liang, H. H., Chiu, H. S., Wee, Y. K., Senabouth, A., Lukowski, S. W., Crombie, D. E., Lidgerwood, G. E., et al. (2021) · Genome biology · doi:10.1186/s13059-021-02293-3 · Cited by 104 · see citing works
“common genetic variation between individuals influences gene expression [1, 2].”
BackgroundWhy the activity of a gene depends on its neighbors
Feuerborn, A., & Cook, P. R. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.07.001 · Cited by 88 · see citing works
Rey, S., Boltaña, S., Vargas, R., Roher, N., & Mackenzie, S. (2013) · Molecular Ecology · doi:10.1111/mec.12556 · Cited by 87 · see citing works
“However, this view, that is, reduction of expression heterogeneity has been challenged on numerous occasions and is counterintuitive if the aim is to understand adaptive phenotypic variation (Raser & O’Shea 2005; Rockman & Kruglyak 2006; Leek & Storey 2007; Mar et al. 2011).”
BackgroundGenetic Influences on Translation in Yeast
Albert, F. W., Muzzey, D., Weissman, J. S., & Kruglyak, L. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004692 · Cited by 72 · see citing works
“Differences in gene expression between individuals can be caused by genetic variants that act in cis or by variants that act in trans [2].”
BackgroundSelf-citationeQTL Mapping Using RNA-seq Data
Sun, W., & Hu, Y. (2012) · Statistics in Biosciences · doi:10.1007/s12561-012-9068-3 · Cited by 77 · see citing works
“trans-eQTLs based on the ASE patterns [63].”
Munger, S. C., Raghupathy, N., Choi, K., Simons, A. K., Gatti, D. M., Hinerfeld, D. A., Svenson, K. L., Keller, M. P., Attie, A. D., Hibbs, M. A., et al. (2014) · Genetics · doi:10.1534/genetics.114.165886 · Cited by 85 · see citing works
“Previous eQTL studies in genetically diverse populations suggest that the most significant eQTL tend to be local (Rockman and Kruglyak 2006; Pickrell et al. 2010; Aylor et al. 2011; Lappalainen et al. 2013).”
BackgroundBlood transcriptomics and metabolomics for personalized medicine
Li, S., Todor, A., & Luo, R. (2015) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2015.10.005 · Cited by 84 · see citing works
“For instance, transcriptomics data can be associated with genomic QTLs (quantitative trait loci) and denoted as expression QTL or “eQTL” [14,90].”
BackgroundInherited Variation in Gene Expression
Skelly, D. A., Ronald, J., & Akey, J. M. (2009) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-082908-150121 · Cited by 76 · see citing works
“Perlstein EO, Ruderfer DM, Ramachandran G, Haggarty SJ, Kruglyak L, Schreiber SL. 2006.”
BackgroundInfluentialZhang, Y.-Y., Yang, Z., He, Y.-Z., Liu, D.-X., Liu, Y.-Y., Liang, C., Xie, M.-L., Jia, Y., Ke, Q., Zhou, Y.-M., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01957-7 · Cited by 83 · see citing works
“3–6), we can expand many examples based on Supplementary Tables 12 and 18.”
Cooley, A. M., Modliszewski, J. L., Rommel, M. L., & Willis, J. H. (2011) · Current Biology · doi:10.1016/j.cub.2011.03.028 · Cited by 78 · see citing works
“regulation [12].”
High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissuesPreprint
Huang, G., Shifman, S., Valdar, W. S. J., Johannesson, M., Yalcin, B., Taylor, M. S., Taylor, J. M., Mott, R., & Flint, J. (2009) · Genome Research · doi:10.1101/gr.088120.108 · Cited by 73 · see citing works
“These studies show that variation in transcript abundance arises from expression quantitative trait loci (eQTL) that can be classified as either local (cis-eQTLs) or distant (trans-eQTLs) regulatory variants (Rockman and Kruglyak 2006).”
BackgroundIdentification of allele-specific alternative mRNA processing via transcriptome sequencing
Li, G., Bahn, J. H., Lee, J., Peng, G., Chen, Z., Nelson, S. F., & Xiao, X. G. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks280 · Cited by 77 · see citing works
“107 626 587 53 162 291 (49) 43 538 740 (40) 1 637 731 (2) 3 312 997 (3) 5 974 828 (6)”
Background
- Authors
- Rockman, M. V., & Kruglyak, L.
- Affiliations
- Princeton University (US)
- Corresponding author
- Kruglyak, Leonid
- Venue
- Nature Reviews Genetics
- Published
- 2006-11
- Volume
- 7
- Issue
- 11
- Pages
- 862-872
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2040912377
- Cited by
- 666
- References
- 0
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 18 · 2023: 19 · 2022: 24 · 2021: 50 · 2020: 27 · 2019: 35 · 2018: 26 · 2017: 29 · 2016: 36 · 2015: 33 · 2014: 41 · 2013: 39 · 2012: 41
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- James S. McDonnell Foundation
- Jane Coffin Childs Memorial Fund for Medical Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- global gene expression, mRNA levels, quantitative traits, transcriptional regulation, regulatory variation, DNA sequence variation, phenotypic variability, gene expression microarrays, linkage analysis, association analysis
- MeSH terms
- Amino Acid Sequence, Animals, Fungal Proteins, Genetic Techniques, Humans, Molecular Sequence Data, Transcription, Genetic, Genetic Variation, Yeasts, Gene Expression, Sequence Homology, Amino Acid, Quantitative Trait Loci
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
