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 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.
Vasiliev
G V
GV
Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, Russia.
Merkulov
V M
VM
Kobzev
V F
VF
Merkulova
T I
TI
Ponomarenko
M P
MP
Kolchanov
N A
NA
D000818:Animals; D001665:Binding Sites; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D006801:Humans; D007438:Introns; D001523:Mental Disorders / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D014157:Transcription Factors; D014366:Tryptophan Oxygenase