Genetics of gene expression surveyed in maize, mouse and man

  title={Genetics of gene expression surveyed in maize, mouse and man},
  author={Eric E. Schadt and Stephanie A. Monks and Thomas A. Drake and Aldons J. Lusis and Nam Che and Veronica V. Colinayo and Thomas G. Ruff and Stephen B. Milligan and John R. Lamb and Guy Cavet and Peter S. Linsley and Mao Mao and Roland B. Stoughton and Stephen H. Friend},
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… 
Expression quantitative trait loci analysis in plants.
This review focuses on eQTL studies in plants, addressing conceptual and technical aspects that include experimental design, genetic polymorphism prediction and candidate gene identification.
Genetic Basis of Transcriptome Diversity in Drosophila melanogaster
High complexity of the genetic control of gene expression is found, including widespread sexual dimorphism, highly modularized expression patterns with involvement of novel RNA transcripts, and frequent epistatic interactions among expression quantitative trait loci (QTLs) which often give rise to variance expression QTLs.
Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease
This work mapped cis- and trans-regulatory control elements for expression of thousands of genes across the genome in the BXH/HXB panel of rat recombinant inbred strains and generated a data set of 73 candidate genes for hypertension that merit testing in human populations.
Systems Genetics of Complex Traits in Drosophila melanogaster
Determining the genetic architecture of complex traits is challenging because phenotypic variation arises from interactions between multiple, environmentally sensitive alleles. We quantified
Multiple Locus Linkage Analysis of Genomewide Expression in Yeast
A new, computationally efficient method for simultaneously mapping multiple gene expression quantitative trait loci that directly uses all of the available data is developed and produces easy-to-interpret measures of statistical significance for both individual loci and the overall joint significance of multiple loci selected for a given expression trait.
Linking Metabolic QTLs with Network and cis-eQTLs Controlling Biosynthetic Pathways
This report has mapped quantitative trait loci–controlling glucosinolate content in a population of 403 Arabidopsis Bay × Sha recombinant inbred lines and found that regulatory connections can feedback from metabolism to transcripts, which suggests that natural variation in transcripts may significantly impact phenotypic variation, but thatnatural variation in metabolites or their enzymatic loci can feed back to affect the transcripts.
Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits
A hybrid procedure to map loci involved in complex traits that leverages the strengths of forward and reverse genetic approaches is detailed and 5-lipoxygenase is identified as underlying previously identified quantitative trait loci in an F2 cross between strains C57BL/6J and DBA/2J and shows that it has pleiotropic effects on body fat, lipid levels and bone density.
Combined Expression Trait Correlations and Expression Quantitative Trait Locus Mapping
It is concluded that trait correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if the authors studied only mRNA traits with statistically significant linkages in this small cross.
Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes
To highlight the usefulness of this much-enlarged map of cis-regulated transcripts for the discovery of genes that influence complex traits in humans, as an example, high-density lipoprotein cholesterol concentration is selected as a phenotype of clinical importance and the cis- regulated vanin 1 (VNN1) gene is identified as harboring sequence variants that influence high- density lipop protein cholesterol concentrations.
An integrative genomics strategy for systematic characterization of genetic loci modulating phenotypes.
This strategy integrates gene-phenotype relations from decades of experimental mutagenesis studies and new genomic resources to provide an approach to rapidly expand knowledge on genetic loci modulating phenotypes.


Quantitative trait loci underlying gene product variation: a novel perspective for analyzing regulation of genome expression.
A methodology to dissect the genetic architecture of quantitative variation of numerous gene products simultaneously might help understanding the architecture of regulatory networks and the possible adaptive or phenotypic significance of the polymorphism of the genes involved.
Quantitative trait loci and metabolic pathways: genetic control of the concentration of maysin, a corn earworm resistance factor, in maize silks.
  • P. Byrne, M. McMullen, E. Coe
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
The results provide evidence that regulatory loci have a central role and that there is a complex interplay among different branches of the flavonoid pathway in the expression of this trait.
Combining mouse congenic strains and microarray gene expression analyses to study a complex trait: the NOD model of type 1 diabetes.
The results suggest that the dramatic disease protection conferred by six Idd loci cannot be rationalized in terms of global effects on the noninduced immune system and have important implications for the design of future microarray-based studies in T1D and, more generally, for studies that aim to combine genome-wide expression profiling and congenic mapping.
Genetic Dissection of Transcriptional Regulation in Budding Yeast
To begin to understand the genetic architecture of natural variation in gene expression, we carried out genetic linkage analysis of genomewide expression patterns in a cross between a laboratory
Genetic dissection of the relationship between carbon metabolism and early growth in maize, with emphasis on key-enzyme loci
The strong correlation between growth rate and invertase activity could be explained to a large extent by a single region of chromosome 8, and the possible role of the polymorphism of key-enzyme genes in physiological processes, and hence in maize growth.
A generalization of the mixture model in the mapping of quantitative trait loci for progeny from a biparental cross of inbred lines.
An approach for the generalization of the mixture model for progeny from a single bi-parental cross of inbred lines is developed and can easily be combined with current QTL mapping approaches.
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.
Analysis of NZB/BINJ x SM/J intercross mice located a quantitative trait locus (QTL) for obesity on distal mouse chromosome 2, in a region syntenic with a large region of human chromosome 20, showing linkage to percent body fat and fat mass.
Robust variance-components approach for assessing genetic linkage in pedigrees.
  • C. Amos
  • Mathematics
    American journal of human genetics
  • 1994
To assess evidence for genetic linkage from pedigrees, a limited variance-components approach is developed and it is shown that the size of likelihood-ratio tests was appropriate but that the monogenic component of variance was generally underestimated by the likelihood approach.
Functional Discovery via a Compendium of Expression Profiles
Mouse nicotinamide N-methyltransferase gene: molecular cloning, structural characterization, and chromosomal localization.
Cloning and structural characterization of the mouse NNMT gene will make it possible to study molecular genetic mechanisms involved in the expression of this important methyltransferase.