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E. E. Geisert, L. Lu, W. Gu, R. W. Williams; Covariance of mRNA Identifies Genetic Networks in the Eye. Invest. Ophthalmol. Vis. Sci. 2008;49(13):6091.
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The Hamilton Eye Institute Mouse Database (HEIMED) is a project that uses the genetic covariance in the BXD recombinant inbred (RI) strains of mice and traditional inbred strains to identify cellular signatures at the transcript level and genetic networks in the tissues of the mouse eye.
Traditionally, the BXD RI strain set was as a tool to map genomic loci controlling physical traits such brain weight or neuron number. Our group has used the reference panel of mice to unravel genetic networks controlling genetic networks in the eye. By treating the naturally occurring changes in mRNA levels as a phenotype, the genomic loci modulating the dif¬fer¬ences in tran¬scriptional control can be evaluated using traditional QTL mapping methods.
The HEIMED estimates of mRNA expression in whole eyes of 85 lines of young adult mice (including 64 BXD RI strains) generated using 132 Affymetrix M430 2.0 arrays. The variations in the level of a single transcript can be correlated with the levels of over 36,000 transcripts identified by the Affymetrix M430 2.0 array, from producing genetic networks, as well as transcriptome signatures of cells and tissues. This ap¬proach can lead to dissection of entire networks of genes that are parts of the trans¬criptional changes under¬lying the development of the eye. Specific examples include a unique genetic signature for cell types such as rods or tissue types such as cornea.
To bring this power of the expression genetics and the BXD RI strain set to the study of the eye, we developed the HEIMED. The BXDs are particularly useful for systems genetics because both parental strains have been sequenced (8x coverage of B6 and 1.5x coverage of D2). Physical maps in GeneNetwork incorporate approximately 2 million B6 vs D2 SNPs from Celera Genomics and from the Perlegen-NIEHS sequencing effort.
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