One potential stumbling block to the development of this knowledge base is that technologies to assess the function of these regulatory elements in the intact human CNS do not exist. However, it is well established that lymphoblast cell lines, which are more readily obtained, are valuable tools for deciphering the effects of genetic variation on gene expression [Hranilovic et al., 2004; Bradley et al., 2005; Shukla and Dolan, 2005; Arenas et al., 2007]. In addition, we and others have recently shown that lymphoblast cell lines derived from human subjects retains transcriptional signatures reflective of the clinical status of their donors [Vawter et al., 2004; Philibert et al., 2007b,c]. Hence, by using these in vitro cell lines from well-characterized subjects as surrogates for in vivo CNS cells, it may be possible to delineate the identity of the regulatory elements and determine whether epigenetic effects on these elements affect their function in neuropsychiatric illness.
