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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.

bmc genomics

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