Mapping of trans-acting regulatory factors from microarray data.
To explore the mapping of factors regulating gene expression, we have carried out linkage studies using expression data from individual transcripts (from Affymetrix microarrays; Genetic Analysis Workshop 15 Problem 1) and composite data on correlated groups of transcripts. Quality measures for the arrays were used to remove outliers, and arrays with sex mismatches were also removed. Data likely to represent noise were removed by setting a minimum threshold of present calls among the non-redundant set of 190 arrays. SOLAR was used for genetic analysis, with MAS5 signal as the measure of expression. Probe sets with larger CVs generated more linkages (LOD > 2.0). While trans linkages predominated, linkages with the largest LOD scores (>4) were mostly cis. Hierarchical clustering was used to generate correlated groups of genes. We tested four composite measures of expression for the clusters. The average signal, average normalized signal, and the first principal component of the data behaved similarly; in 8/19 clusters tested, the composite measures linked to a region to which some individual probe sets within the cluster also linked. The second principal component only produced one linkage with LOD > 2. One cluster based upon chromosomal location, containing histone genes, linked to two trans regions. This work demonstrates that composite measures for genes with correlated expression can be used to identify loci that affect multiple co-expressed genes.
McClintick
Jeanette N
JN
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, Indiana 46202, USA.|Center for Medical Genomics at Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, Indiana 46202, USA.
Liu
Yunlong
Y
Department of Medicine, Indiana University School of Medicine, 714 North Senate Avenue, EF250G, Indianapolis, Indiana 46202, USA.|Center for Medical Genomics at Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, Indiana 46202, USA.
Edenberg
Howard J
HJ
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, Indiana 46202, USA.|Center for Medical Genomics at Indiana University School of Medicine, 635 Barnhill Drive, MS4063, Indianapolis, Indiana 46202, USA.