Please use this identifier to cite or link to this item: https://hdl.handle.net/1959.11/7563
Title: 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
Contributor(s): Noyes, Harry A (author); Agaba, Morris (author); Anderson, Susan (author); Archibald, Alan L (author); Brass, Andy (author); Gibson, John  (author); Hall, Laurence (author); Hulme, Helen (author); Oh, Sung Jong (author); Kemp, Stephen (author)
Publication Date: 2010
DOI: 10.1186/1471-2164-11-361
Handle Link: https://hdl.handle.net/1959.11/7563
Abstract: Background: Differences 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. Results: To 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. Conclusions: The 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.
Publication Type: Journal Article
Source of Publication: BMC Genomics, 11(361), p. 1-11
Publisher: BioMed Central Ltd
Place of Publication: United Kingdom
ISSN: 1471-2164
Fields of Research (FoR) 2008: 060406 Genetic Immunology
060405 Gene Expression (incl Microarray and other genome-wide approaches)
060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics)
Socio-Economic Objective (SEO) 2008: 920109 Infectious Diseases
830302 Dairy Cattle
830301 Beef Cattle
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article

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