Point mutations within 663-666 bp of intron 6 of the human TDO2 gene, associated with a number of psychiatric disorders, damage the YY-1 transcription factor binding site

Single base mutations G --> A at position 663 and G --> T at position 666 o f intron 6 of the human tryptophan oxygenase gene (TDO2) are associated wit h a variety of psychiatric disorders [Comings, D.E. ct al. (1996) Pharmacog enetics 6, 307-318], Binding of rat liver nuclear extract proteins to synth etic double-strand oligonucleotides corresponding to three allelic states o f the region between 651 bp and 680 bp of human TDO2 intron 6 has been stud ied by gel shift assay. It has been demonstrated that to each allelic state of the region there corresponds a specific set of proteins that interacts with it. With the aid of computer analysis and using specific anti-YY-l ant ibodies it has been shown that both mutations damage the YY-1 transcription factor binding site. (C) 1999 Federation of European Biochemical Societies .