Construction of genome-wide genetic interaction networks from mammalian radiation hybrid genotyping data

Interactions, in which a gene's effect is dependent on its functional relationships with other genes, are an important determinant of phenotypic variation. Yet, only a tiny fraction of the vast number of interactions has been explored experimentally, particularly in mammals, so our understanding of their contributions is feeble. Radiation hybrid panel genotyping efforts have provided data in which it is possible to identify genes that are retained together more or less than would be expected by chance and constitute potential interactions. From these data we mapped hundreds of thousands of interactions. Furthermore, combining radiation hybrid datasets provided enough power to identify millions of potential interactions in the mammalian genome. Gene interaction networks constructed from individual radiation hybrid datasets overlapped strongly with each other. We found more limited overlap between networks constructed from combined radiation hybrid datasets and a protein-protein interaction network derived the Human Protein Reference Database. Our results suggest that genetic interaction and physical interaction networks are largely orthogonal, as has been found previously (Tong et al., 2004) (Ahn, In Press). More generally, this study verifies that a large number of potential genetic interactions covering nearly the entire mammalian genome can be identified quickly and inexpensively in publicly available data.