STRUCTURAL ORGANIZATION OF THE HUMAN FLAVIN-CONTAINING MONOOXYGENASE-3 GENE (FMO3), THE FAVORED CANDIDATE FOR FISH-ODOR SYNDROME, DETERMINED DIRECTLY FROM GENOMIC DNA

The inherited metabolic disorder trimethylaminuria (fish-odor syndrome ) is associated with defective hepatic N-oxidation of dietary-derived trimethylamine catalyzed by flavin-containing monooxygenase (FMO). As FMO3 encodes the major form of FMO expressed in adult human liver, it represents the best candidate gene for the disorder. The structural or ganization of FMO3 was determined by sequencing the products of exon-t o-exon and vectorette PCR, the latter through the use of vectorette li braries constructed directly from genomic DNA. The gene contains one n oncoding and eight coding exons. Knowledge of the exon/intron organiza tion of the human FMO3 gene enabled each of the coding exons of the ge ne, together with their associated flanking intron sequences, to be am plified from genomic DNA and will thus facilitate the identification o f mutations in FMO3 in families affected with fish-odor syndrome. (C) 1997 Academic Press.