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

• DOI: 10.1016/s0014-5793(99)01513-6
• Publication Date: 2002-07-25T15:03:33Z
• Authors: Gennady V Vasiliev; Vasily M Merkulov; Viktor F Kobzev; Tatyana I Merkulova; Mikhail P Ponomar...; Nikolay A Kolchanov
• Keywords: 0303 health sciences; Binding Sites; Mental Disorders; Psychiatric disorder; Introns; Tryptophan Oxygenase; Rats; 3. Good health; Binding site; DNA-Binding Proteins; 03 medical and health sciences; YY-1 transcription factor; Mutation; Animals; Erythroid-Specific DNA-Binding Factors; Humans; Point Mutation; Tryptophan oxygenase gene; DNA Damage; Transcription Factors

Single base mutations G→A at position 663 and G→T at position 666 of intron 6 of the human tryptophan oxygenase gene (TDO2) are associated with a variety of psychiatric disorders [Comings, D.E. et al. (1996) Pharmacogenetics 6, 307–318]. Binding of rat liver nuclear extract proteins to synthetic double‐strand oligonucleotides corresponding to three allelic states of the region between 651 bp and 680 bp of human TDO2 intron 6 has been studied 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‐1 antibodies it has been shown that both mutations damage the YY‐1 transcription factor binding site.