Characterization of the Human Dihydropyrimidine Dehydrogenase Gene

摘要: Dihydropyrimidine dehydrogenase (DPD) catabolizes endogenous pyrimidines and pyrimidine-based antimetabolite drugs. A deficiency in human DPD is associated with congenital thymine-uraciluria pediatric patients severe 5-fluorouracil toxicity cancer patients. The dihydropyrimidine gene (DPYD) was isolated, its physical map exon-intron organization were determined by analysis of P1, PAC, BAC, YAC clones. DPYD found to contain 23 exons ranging size from 69 bp (exon 15) 961 23). derived a clone indicated that at least 950 kb length 3 coding sequence an average intron about 43 kb. previously reported 5' donor splice site mutation present can now be assigned exon 14. All sequenced series DNA samples, three point mutations identified racial groups as G1601A 13, Ser534Asn), A1627G Ile543Val), G2194A 18, Val732Ile). These studies, which have established the unusually large, lay framework for uncovering new are responsible fluoropyrimidine