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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
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
BMC Genomics, Volume 11, No. 1, Article 361, Year 2010
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Description
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. © 2010 Noyes et al; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2896378/bin/1471-2164-11-361-S1.TXT
https://efashare.b-cdn.net/share/pmc/articles/PMC2896378/bin/1471-2164-11-361-S2.TXT
https://efashare.b-cdn.net/share/pmc/articles/PMC2896378/bin/1471-2164-11-361-S3.TXT
https://efashare.b-cdn.net/share/pmc/articles/PMC2896378/bin/1471-2164-11-361-S4.XLS
https://efashare.b-cdn.net/share/pmc/articles/PMC2896378/bin/1471-2164-11-361-S5.TXT
https://efashare.b-cdn.net/share/pmc/articles/PMC2896378/bin/1471-2164-11-361-S6.DOC
https://efashare.b-cdn.net/share/pmc/articles/PMC2896378/bin/1471-2164-11-361-S7.TXT
Authors & Co-Authors
Noyes, Harry A.
United Kingdom, Liverpool
University of Liverpool
Agaba, Morris K.
Kenya, Nairobi
International Livestock Research Institute Nairobi
Anderson, Susan
United Kingdom, Roslin
The Royal Dick School of Veterinary Studies
Archibald, Alan L.
United Kingdom, Roslin
The Royal Dick School of Veterinary Studies
Brass, A.
United Kingdom, Manchester
The University of Manchester
Gibson, J. P.
Kenya, Nairobi
International Livestock Research Institute Nairobi
Australia, Armidale
University of new England Australia
Hall, Laurence S.
United Kingdom, Roslin
The Royal Dick School of Veterinary Studies
Hulme, Helen
United Kingdom, Manchester
The University of Manchester
Oh, Sung-jong
South Korea, Jeonju
Rural Development Administration
Kemp, Stephen J.
United Kingdom, Liverpool
University of Liverpool
Kenya, Nairobi
International Livestock Research Institute Nairobi
Statistics
Citations: 10
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1186/1471-2164-11-361
e-ISSN:
14712164
Research Areas
Genetics And Genomics