Our results show that Hnf4a deletion spontaneously triggered chronic inflammatory response in the colon characterized by disrupted crypt architecture, proliferative changes, apoptosis, increased inflammatory mediator secretion and increased immune cell infiltration. We propose that the loss of mucosal homeostasis is initiated by an early reduction of mucosal ion transport, which was not associated with a significant change of barrier permeability. Claudin-15, a paracellular ion transporter,Fingolimod was confirmed to be a novel and direct gene target for Hnf4a. These findings identify Hnf4a as a transcriptional regulator of ion transport and support a novel functional role for this transcriptional regulator in colonic inflammatory homeostasis. The overall mutation frequency was higher in this meta-analysis than the current study. Mutation frequency in the meta-analysis might have been high, in part, due to the publication bias against negative mutational data, the employment of functional knowl-
edge-based subject locus selection in many reports, and absence of
consideration to germline polymorphism level in many reports.
Germline variation prevalence was not significantly dependent on
microsatellite length within our short microsatellite group;
however,ICI 182780 a significant microsatellite length dependency of germ-
line variation prevalence was observed when our data were
compared to previously studied groups of longer 39UTR microsatellites. In yeast, repeat number and
repeat unit size dictate the susceptibility to DNA strand slippage
and microsatellite instability. Thus, our observations
confirm that susceptibility to DNA strand slippage is the
determinant of length polymorphism in the majority of 39UTR
microsatellites in both MMR-deficient and-proficient settings in
humans., 2) significant RB1CC1 mRNA overexpression was In the current study, we assessed interspecies sequence conservation level and proximity to some genetic elements as indicators of the potential relevance of a microsatellite to the posttranscriptional functional integrity of the corresponding gene.