An active version of the SRF co-activator MAL induced reporter gene activity in these cells, however, unlike to cell lines expressing BRM, the co-expression of SCAI did not affect the MAL-induced reporter gene activity in these cells, indicating that SCAI may be functionally dependent on SWI/SNF-activity to mediate changes in gene expression. We could further show that the expression of an ATPase-deficient mutant of BRM can relieve the inhibition of SCAI on MALinduced SRF-dependent reporter-activity. This effect was specific for SCAI, since the repression mediated by a dominant negative version of MAL, a construct that binds to SRF but lacks the transactivation domain, was not affected by co-expression of BRM K749R. In addition, we were able to show that siRNA-mediated silencing of BRM abolishes the effect of SCAI on MAL-SRF transcriptional activity, further supporting our hypothesis of a functional hierarchy between BRM and SCAI. It is at present also not clear whether SCAI can directly modulate the activity of BRM containing SWI/SNF complexes or whether SCAI represents a novel auxiliary factor that mediates recruitment of the complex to specific chromosomal locations. We next analyzed the functional consequences of this interaction for tumor cell invasion. Our data show that silencing of BRM as also SCAI caused an increase of cell invasion of MDA-MB-435 as well as MDA-MB-231 cells into 3Dmatrigel matrices. The moderate effects on cell invasion after siRNA treatment in MDA-MB-231 cells could be explained by the high basal invasion of +/240%, whereas MDA-MB-435 cells show a basal invasion of +/25%. These data further supports our hypothesis, that both proteins are functionally linked to each other and may modulate the expression of target genes, which are critical for the invasive behavior of tumor cells. Taken together, our current data show that SCAI and the SWI/ SNF complex interact physically and control gene expression in human cancer cells to regulate invasive cell migration. Our data further indicate that SCAI is functionally dependent on BRM expression, indicating that SWI/SNF could be a downstream mediator for SCAI signaling. The expression analysis of human tumor samples revealed that downregulation of SCAI, like BRM within 97 nuclear families using the TDT test. In addition to the Linkage GWAS we explored gene-gene interactions and pathway 
analyses. We also performed a non-parametric linkage analysis and compared the results with the published linkage analysis, with microsatellite markers, performed in the same set of families previously. Furthermore, quantitative PCR was used to investigate levels of gene expression in small intestinal biopsies from additional patients with CD autoimmunity and control patients. Finally, we stratified the TDT analysis on HLA genotype. It has been shown that carrying DQB1*02 on both chromosomes, confers higher risk of developing CD as compared to heterozygote individuals.