An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells

Variable number tandem repeats (VNTR) within noncoding regions of a number of genes have been correlated with susceptibility to various disease states . In particular, a VNTR polymorphism of a 16 or 17 bp element within intron 2 of the human serotonin transporter gene has been correlated with a predi sposition to affective disorders. We have demonstrated that this region wil l support differential levels of reporter gene expression in differentiatin g embryonic stem cells, this being dependent on the presence of 10 or 12 co pies of the repeat. The VNTR domain can therefore act as a transcriptional regulator, a property which potentially contributes to disease susceptibili ty. (C) 1999 Federation of European Biochemical Societies.