Journal
NATURE GENETICS
Volume 37, Issue 11, Pages 1224-1233Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng1619
Keywords
-
Categories
Ask authors/readers for more resources
Forward genetic approaches to identify genes involved in complex traits such as common human diseases have met with limited success. Fine mapping of linkage regions and validation of positional candidates are time-consuming and not always successful. Here we detail a hybrid procedure to map loci involved in complex traits that leverages the strengths of forward and reverse genetic approaches. By integrating genotypic and expression data in a segregating mouse population, we show how clusters of expression quantitative trait loci linking to regions of the genome accurately reflect the underlying perturbation to the transcriptional network induced by DNA variations in genes that control the complex traits. By matching patterns of gene expression in a segregating population with expression responses induced by single-gene perturbation experiments, we show how genes controlling clusters of expression and clinical quantitative trait loci can be mapped directly. We demonstrate the utility of this approach by identifying 5-lipoxygenase as underlying previously identified quantitative trait loci in an F-2 cross between strains C57BL/6J and DBA/2J and showing that it has pleiotropic effects on body fat, lipid levels and bone density.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available