GENOMIC STRUCTURE AND POLYMORPHISM OF THE HUMAN THROMBOXANE SYNTHASE-ENCODING GENE

Thromboxane synthase (TS) is a cytochrome P-450 (CYP450) enzyme cataly zing the conversion of prostaglandin endoperoxide (PGH(2)) into thromb oxane A(2) (TxA(2)) which plays a crucial role in hemostasis and cardi ovascular diseases, Twelve genomic clones containing the DNA encoding the human TS gene (hTS) were isolated and characterized to determine t he exon/intron boundaries and restriction maps of the nearly contiguou s structure of the gene, The hTS contains 13 exons spanning more than 150 kb, Its first five exons, divided by relatively large introns, spr ead over 100 kb, but encode less than one third of the full-length TS transcript, Southern analysis indicates that the human haploid genome contains a single copy of the TS gene. Although multiple transcription start points (tsp) are utilized, transcription of hTS is primarily TA TA-independent, as determined by promoter-directed reporter gene expre ssion in transfected cells. A dinucleotide (CA) repetitive sequence id entified in the ninth intron of the gene exhibits allelic polymorphism . At least four distinctive alleles, containing from 13 to 20 copies o f the CA repeats, have been detected.