ArticleBMC genomics2010
Genotype and expression analysis of two inbred mouse strains and two derived congenic strains suggest that most gene expression is trans regulated and sensitive to genetic background.
Article in BMC genomics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- Streamlined computational pipeline for genetic background characterization of genetically engineered mice based on next generation sequencing data.BMC genomics · 2019Article
- Combining genetic mapping with genome-wide expression in experimental autoimmune encephalomyelitis highlights a gene network enriched for T cell functions and candidate genes regulating autoimmunity.Human molecular genetics · 2013Article
- Identification of a loss-of-function mutation in Ube2l6 associated with obesity resistance.Diabetes · 2013Article
- Prioritization of SNPs for genome-wide association studies using an interaction model of genetic variation, gene expression, and trait variation.Molecules and cells · 2012Article
- Strict control of transgene expression in a mouse model for sensitive biological applications based on RMCE compatible ES cells.Nucleic acids research · 2011Article
- Global analysis of gene expression in the developing brain of Gtf2ird1 knockout mice.PloS one · 2011Article
- A comprehensive genetic analysis of candidate genes regulating response to Trypanosoma congolense infection in mice.PLoS neglected tropical diseases · 2010Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundDifferences in gene expression may be caused by nearby DNA polymorphisms (cis regulation) or by interactions of gene control regions with polymorphic transcription factors (trans regulation). Trans acting loci are much harder to detect than cis acting loci and their effects are much more sensitive to genetic background.
resultsTo quantify cis and trans regulation we correlated haplotype data with gene expression in two inbred mouse strains and two derived congenic lines. Upstream haplotype differences between the parental strains suggested that 30-43% of differentially expressed genes were differentially expressed because of cis haplotype differences. These cis regulated genes displayed consistent and relatively tissue-independent differential expression. We independently estimated from the congenic mice that 71-85% of genes were trans regulated. Cis regulated genes were associated with low p values (p < 0.005) for differential expression, whereas trans regulated genes were associated with values 0.005 < p < 0.05. The genes differentially expressed between congenics and controls were not a subset of those that were differentially expressed between the founder lines, showing that these were dependent on genetic background. For example, the cholesterol synthesis pathway was strongly differentially expressed in the congenic mice by indirect trans regulation but this was not observable in the parental mice.
conclusionsThe evidence that most gene regulation is trans and strongly influenced by genetic background, suggests that pathways that are modified by an allelic variant, may only exhibit differential expression in the specific genetic backgrounds in which they were identified. This has significant implications for the interpretation of any QTL mapping study.
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