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 non-coding 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 predisposition to affective disorders. We have demonstrated that this region will support differential levels of reporter gene expression in differentiating embryonic stem cells, this being dependent on the presence of 10 or 12 copies of the repeat. The VNTR domain can therefore act as a transcriptional regulator, a property which potentially contributes to disease susceptibility.
Fiskerstrand
C E
CE
Department of Veterinary Pathology, University of Edinburgh, UK.
Lovejoy
E A
EA
Quinn
J P
JP
D000483:Alleles; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D026901:Membrane Transport Proteins; D018598:Minisatellite Repeats / Q000235:genetics*; D019964:Mood Disorders / Q000235:genetics*; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D014212:Tretinoin