Genomic organization of the 3 ' region of the human thyroglobulin gene

The genomic organization of the 3' end of the human Thyroglobulin (Tg) gene has not previously been characterized. We isolated and characterized seven teen lambda phage clones from a human genomic library that included nucleot ides 6263 to 8410 of the Tg mRNA, encompassing the last thirteen 3' exons o f the Tg gene. The region contained exons ranging in size from 94 to 222 nu cleotides, split by introns of 1 to 64 kb. We estimate a total of 48 exons in the Tg gene. All the intron-exon boundaries were sequenced. We found tha t the splicing sequences diverged considerably from the 3' and 5' consensus . However, the GT-AG rule was perfectly respected in all the exons. A total of 5788 intronic bases and most of the sequences contained in the 13 exons were analyzed (1846 bases). One sequence variation, TT to CC at positions 8377-8378, was found in the 3' untranslated segment. The three tyrosine res idues involved in thyroid hormones synthesis (amino acids 2554, 2568, and 2 747) at the carbosyl termini of Tg, are encoded by exons 44, 45, and 48. Th e knowledge of the precise organization of the Tg gene should help to direc t studies of Tg gene mutations in families in which a defect in the synthes is of Tg occurs.