Confidence intervals for putative quantitative trait loci – development and applications of new linkage methods

A new method for constructing confidence intervals for the location of putative genes regulating expression levels (quantitative traits) is proposed. This method is suitable for the "intermediate" fine-mapping step usually performed between the initial whole-genome screening and the follow-up fine mapping step as a means of reducing the size of the region where the latter is performed. Assuming the existence of a single quantitative trait locus (QTL) in the region/chromosome identified by the genome scan, the method constructs a confidence region for its true position by testing each location in the chromosome to see if it can be the trait locus. We applied our method to the gene expression data from Problem 1 of Genetic Analysis Workshop 15 (GAW15) data, focusing on 25 genes that have previously been shown to share common regulating factor(s) on chromosome 14. Our results pointed to the same region on chromosome 14 for 13 of the gene expressions studied, not only partially reproducing the results of the previous analysis, but also yielding 95% confidence regions for the regulatory quantitative trait loci. Moreover, we identified three regions, one on each of the chromosomes 3, 9, and 13, which potentially harbor additional common QTLs for several of the original gene expressions.