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We have cloned overlapping segments of the human thyroglobulin gene from a genomic cosmid library. Restriction mapping and electron microscopy show that a region of 38 kb at or near the 3'-end of this gene encodes only 850 nucleotides or 10% of the messenger RNA (mRNA) sequence. The region contains five exons of 130-210 nucleotides, split by introns of 1 to 15-17 kb. This represents the lowest ratio of coding to non-coding DNA (2.2%) found thus far in any eukaryotic gene. Blot hybridization under non-stringent conditions shows the presence of only one copy of this gene in the human genome and the absence of other closely related sequences.

The human thyroglobulin gene contains two 15-17 kb introns near its 3′-end