Neurologically relevant genes modulated in brain tissue by a trans-regulatory QTL (quantitative trait locus) near D6Mit150 marker.
Full description or abstract
Patterns of gene expression in the central nervous system are highly variable and heritable. This genetic variation among normal individuals leads to considerable structural, functional and behavioral differences. We devised a general approach to dissect genetic networks systematically across biological scale, from base pairs to behavior, using a reference population of recombinant inbred strains. We profiled gene expression using Affymetrix oligonucleotide arrays in the BXD recombinant inbred strains, for which we have extensive SNP and haplotype data. We integrated a complementary database comprising 25 years of legacy phenotypic data on these strains. Covariance among gene expression and pharmacological and behavioral traits is often highly significant, corroborates known functional relations and is often generated by common quantitative trait loci. We found that a small number of major-effect quantitative trait loci jointly modulated large sets of transcripts and classical neural phenotypes in patterns specific to each tissue. We developed new analytic and graph theoretical approaches to study shared genetic modulation of networks of traits using gene sets involved in neural synapse function as an example. We built these tools into an open web resource called WebQTL that can be used to test a broad array of hypotheses.
Collection
C2: Curated CGP: Chemical and Genetic Perturbations
