International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Manly KF, Wang J, Williams RW

University of Tennessee Health Science Center, Memphis, TN, United States

Heritable differences in transcribed RNA levels can be mapped as quantitative trait loci (QTLs). One source of data is microarray analysis of RNA transcripts in a set of recombinant inbred lines, such as that available at the WebQTL Web site, QTL Reaper is software for rapid detection of QTLs in large data sets. It estimates empirical p-values by permutation tests, adapting the number of permutations to the significance of the QTL. The resulting p-values lend themselves to modern multiple-test statistical methods, which can define statistically significant sets of QTLs without excessive numbers of either false positives or false negatives.

Recent work with QTL Reaper has focused on improving methods for combining data from individual transcript-specific oligonucleotide probes. The use of recombinant inbred lines allows replicate measurements on genetically identical individuals, and replicates allow an estimate of the heritability of expression measured by individual oligonucleotide probes. This heritability varies greatly among probes, even among those designed to measure the same transcript. Since heritability is necessary (but not sufficient) to define a QTL, we have tested heritability-weighted averages to define expression of a transcript, averages in which each probe value is weighted by the heritability of that probe relative to the average heritability in the probe set. These averages allow detection of more QTLs than several other methods.

Supported by: Dunavant Chair, UTHSC, Center of Genomics and Bioinformatics, and the Human Brain Project (MH62009, NIMH)

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