DNA variation and brain region-specific expression profiles exhibit different relationships between inbred mouse strains: implications for eQTL mapping studies.
BACKGROUND
Expression quantitative trait locus (eQTL) mapping is used to find loci that are responsible for the transcriptional activity of a particular gene. In recent eQTL studies, expression profiles were derived from either homogenized whole brain or collections of large brain regions. However, the brain is a very heterogeneous organ, and expression profiles of different brain regions vary significantly. Because of the importance and potential power of eQTL studies in identifying regulatory networks, we analyzed gene expression patterns in different brain regions from multiple inbred mouse strains and investigated the implications for the design and analysis of eQTL studies.


RESULTS
Gene expression profiles of five brain regions in six inbred mouse strains were studied. Few genes exhibited a significant strain-specific expression pattern, whereas a large number of genes exhibited brain region-specific patterns. We constructed phylogenetic trees based on the expression relationships between the strains and compared them with a DNA-level relationship tree. The trees based on the expression of strain-specific genes were constant across brain regions and mirrored DNA-level variation. However, the trees based on region-specific genes exhibited a different set of strain relationships, depending on the brain region. An eQTL analysis showed enrichment of cis-acting regulators among strain-specific genes, whereas brain region-specific genes appear to be mainly regulated by trans-acting elements.


CONCLUSIONS
Our results suggest that many regulatory networks are highly brain region specific and indicate the importance of conducting eQTL mapping studies using data from brain regions or tissues that are physiologically and phenotypically relevant to the trait of interest.
Hovatta
Iiris
I
The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. iiris.hovatta@ktl.fi
Zapala
Matthew A
MA
Broide
Ron S
RS
Schadt
Eric E
EE
Libiger
Ondrej
O
Schork
Nicholas J
NJ
Lockhart
David J
DJ
Barlow
Carrolee
C
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping / Q000379:methods*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D014644:Genetic Variation; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D040641:Quantitative Trait Loci; D012044:Regression Analysis