Gene expression in the mouse eye: an online resource for genetics using 103 strains of mice.
OBJECTIVE
Individual differences in patterns of gene expression account for much of the diversity of ocular phenotypes and variation in disease risk. We examined the causes of expression differences, and in their linkage to sequence variants, functional differences, and ocular pathophysiology.


METHODS
mRNAs from young adult eyes were hybridized to oligomer microarrays (Affymetrix M430v2). Data were embedded in GeneNetwork with millions of single nucleotide polymorphisms, custom array annotation, and information on complementary cellular, functional, and behavioral traits. The data include male and female samples from 28 common strains, 68 BXD recombinant inbred lines, as well as several mutants and knockouts.


RESULTS
We provide a fully integrated resource to map, graph, analyze, and test causes and correlations of differences in gene expression in the eye. Covariance in mRNA expression can be used to infer gene function, extract signatures for different cells or tissues, to define molecular networks, and to map quantitative trait loci that produce expression differences. These data can also be used to connect disease phenotypes with sequence variants. We demonstrate that variation in rhodopsin expression efficiently predicts candidate genes for eight uncloned retinal diseases, including WDR17 for the human RP29 locus.


CONCLUSIONS
The high level of strain variation in gene expression is a powerful tool that can be used to explore and test molecular networks underlying variation in structure, function, and disease susceptibility. The integration of these data into GeneNetwork provides users with a workbench to test linkages between sequence differences and eye structure and function.
Geisert
Eldon E
EE
Department of Ophthalmology and Center for Vision Research, Memphis, TN 38163, USA. egeisert@utmem.edu
Lu
Lu
L
Freeman-Anderson
Natalie E
NE
Templeton
Justin P
JP
Nassr
Mohamed
M
Wang
Xusheng
X
Gu
Weikuan
W
Jiao
Yan
Y
Williams
Robert W
RW
D000818:Animals; D004198:Disease Susceptibility; D005123:Eye / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D020407:Internet; D008297:Male; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger