Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility.

Background: Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome.

An extracellular region of Serrate is essential for ligand-induced cis-inhibition of Notch signaling.

Cell-to-cell communication via the Notch pathway is mediated between the membrane-bound Notch receptor and either of its canonical membrane-bound ligands Delta or Serrate. Notch ligands mediate receptor transactivation between cells and also mediate receptor cis-inhibition when Notch and ligand are co-expressed on the same cell. We demonstrate in Drosophila that removal of any of the EGF-like repeats (ELRs) 4, 5 or 6 results in a Serrate molecule capable of transactivating Notch but exhibiting little or no Notch cis-inhibition capacity.