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. 1986 Jul 11;14(13):5171–5186. doi: 10.1093/nar/14.13.5171

The human thyroglobulin gene is over 300 kb long and contains introns of up to 64 kb.

F Baas, G J van Ommen, H Bikker, A C Arnberg, J J de Vijlder
PMCID: PMC311533  PMID: 3016640

Abstract

Thyroglobulin (Tg), the precursor of thyroid hormones, is a 660.000 Da dimeric glycoprotein synthesized exclusively in the thyroid gland. We have cloned the human thyroglobulin gene from cosmid and phage libraries and constructed a complete restriction map. The gene encodes an 8.7 kb mRNA, covers at least 300 kb DNA and contains at least 37 exons separated by large introns of up to 64 kb. A striking difference in structure between the 5' and 3' part of the gene suggests that it is composed of two evolutionarily different regions. The first 30 kb DNA encode 3 kb of the mRNA, yielding an exon:intron ratio of 1:10, whereas the remaining 270 kb encodes 5.7 kb of the mRNA with an exon:intron ratio of 1:47. In thyroid cells, the Tg gene is not rearranged and nuclear RNA homologous with sequences internal to the 64 kb intron is present, suggesting that the Tg gene is transcribed as a 300 kb RNA.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnberg A. C., Van Ommen G. J., Grivell L. A., Van Bruggen E. F., Borst P. Some yeast mitochondrial RNAs are circular. Cell. 1980 Feb;19(2):313–319. doi: 10.1016/0092-8674(80)90505-x. [DOI] [PubMed] [Google Scholar]
  2. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  3. Avvedimento V. E., Musti A. M., Obici S., Cocozza S., Di Lauro R. Structural organization of the 3' half of the rat thyroglobulin gene. Nucleic Acids Res. 1984 Apr 25;12(8):3461–3472. doi: 10.1093/nar/12.8.3461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baas F., Bikker H., Geurts van Kessel A., Melsert R., Pearson P. L., de Vijlder J. J., van Ommen G. J. The human thyroglobulin gene: a polymorphic marker localized distal to C-MYC on chromosome 8 band q24. Hum Genet. 1985;69(2):138–143. doi: 10.1007/BF00293284. [DOI] [PubMed] [Google Scholar]
  5. Baas F., Bikker H., van Ommen G. J., de Vijlder J. J. Unusual scarcity of restriction site polymorphism in the human thyroglobulin gene. A linkage study suggesting autosomal dominance of a defective thyroglobulin allele. Hum Genet. 1984;67(3):301–305. doi: 10.1007/BF00291357. [DOI] [PubMed] [Google Scholar]
  6. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  7. Borst P. Discontinuous transcription and antigenic variation in trypanosomes. Annu Rev Biochem. 1986;55:701–732. doi: 10.1146/annurev.bi.55.070186.003413. [DOI] [PubMed] [Google Scholar]
  8. Brocas H., Christophe D., Pohl V., Vassart G. Cloning of human thyroglobulin complementary DNA. FEBS Lett. 1982 Jan 25;137(2):189–192. doi: 10.1016/0014-5793(82)80346-3. [DOI] [PubMed] [Google Scholar]
  9. Cornish-Bowden A. Are introns structural elements or evolutionary debris? Nature. 1985 Feb 7;313(6002):434–435. doi: 10.1038/313434b0. [DOI] [PubMed] [Google Scholar]
  10. Di Lauro R., Obici S., Condliffe D., Ursini V. M., Musti A., Moscatelli C., Avvedimento V. E. The sequence of 967 amino acids at the carboxyl-end of rat thyroglobulin. Location and surroundings of two thyroxine-forming sites. Eur J Biochem. 1985 Apr 1;148(1):7–11. doi: 10.1111/j.1432-1033.1985.tb08799.x. [DOI] [PubMed] [Google Scholar]
  11. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  12. Gilbert W. Genes-in-pieces revisited. Science. 1985 May 17;228(4701):823–824. doi: 10.1126/science.4001923. [DOI] [PubMed] [Google Scholar]
  13. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  14. Hanahan D., Meselson M. Plasmid screening at high colony density. Gene. 1980 Jun;10(1):63–67. doi: 10.1016/0378-1119(80)90144-4. [DOI] [PubMed] [Google Scholar]
  15. Hood L., Kronenberg M., Hunkapiller T. T cell antigen receptors and the immunoglobulin supergene family. Cell. 1985 Feb;40(2):225–229. doi: 10.1016/0092-8674(85)90133-3. [DOI] [PubMed] [Google Scholar]
  16. Ish-Horowicz D., Burke J. F. Rapid and efficient cosmid cloning. Nucleic Acids Res. 1981 Jul 10;9(13):2989–2998. doi: 10.1093/nar/9.13.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leach D. R., Stahl F. W. Viability of lambda phages carrying a perfect palindrome in the absence of recombination nucleases. 1983 Sep 29-Oct 5Nature. 305(5933):448–451. doi: 10.1038/305448a0. [DOI] [PubMed] [Google Scholar]
  18. Lecocq R. E., Dumont J. E. In vivo and in vitro effects of thyrotropin on ribosomal pattern of dog thyroid. Biochim Biophys Acta. 1973 Mar 19;299(2):304–311. doi: 10.1016/0005-2787(73)90354-7. [DOI] [PubMed] [Google Scholar]
  19. Lejeune P. J., Marriq C., Rolland M., Lissitzky S. Amino acid sequence around a hormonogenic tyrosine residue in the N-terminal region of human thyroglobulin after in vivo and in vitro iodination. Biochem Biophys Res Commun. 1983 Jul 18;114(1):73–80. doi: 10.1016/0006-291x(83)91595-4. [DOI] [PubMed] [Google Scholar]
  20. Malthiéry Y., Lissitzky S. Sequence of the 5'-end quarter of the human-thyroglobulin messenger ribonucleic acid and of its deduced amino-acid sequence. Eur J Biochem. 1985 Feb 15;147(1):53–58. doi: 10.1111/j.1432-1033.1985.tb08717.x. [DOI] [PubMed] [Google Scholar]
  21. Marriq C., Rolland M., Lissitzky S. Structure-function relationship in thyroglobulin: amino acid sequence of two different thyroxine-containing peptides from porcine thyroglobulin. EMBO J. 1982;1(4):397–401. doi: 10.1002/j.1460-2075.1982.tb01181.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mercken L., Simons M. J., De Martynoff G., Swillens S., Vassart G. Presence of hormonogenic and repetitive domains in the first 930 amino acids of bovine thyroglobulin as deduced from the cDNA sequence. Eur J Biochem. 1985 Feb 15;147(1):59–64. doi: 10.1111/j.1432-1033.1985.tb08718.x. [DOI] [PubMed] [Google Scholar]
  24. Mercken L., Simons M. J., Swillens S., Massaer M., Vassart G. Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA. Nature. 1985 Aug 15;316(6029):647–651. doi: 10.1038/316647a0. [DOI] [PubMed] [Google Scholar]
  25. Musti A. M., Avvedimento E. V., Polistina C., Ursini V. M., Obici S., Nitsch L., Cocozza S., Di Lauro R. The complete structure of the rat thyroglobulin gene. Proc Natl Acad Sci U S A. 1986 Jan;83(2):323–327. doi: 10.1073/pnas.83.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rawitch A. B., Chernoff S. B., Litwer M. R., Rouse J. B., Hamilton J. W. Thyroglobulin structure-function. The amino acid sequence surrounding thyroxine. J Biol Chem. 1983 Feb 25;258(4):2079–2082. [PubMed] [Google Scholar]
  27. Rawitch A. B., Litwer M. R., Gregg J., Turner C. D., Rouse J. B., Hamilton J. W. The isolation of identical thyroxine containing amino acid sequences from bovine, ovine and porcine thyroglobulins. Biochem Biophys Res Commun. 1984 Jan 30;118(2):423–429. doi: 10.1016/0006-291x(84)91320-2. [DOI] [PubMed] [Google Scholar]
  28. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  29. Rogers J. Exon shuffling and intron insertion in serine protease genes. Nature. 1985 Jun 6;315(6019):458–459. doi: 10.1038/315458a0. [DOI] [PubMed] [Google Scholar]
  30. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sato S., Hutchinson C. A., 3rd, Harris J. I. A thermostable sequence-specific endonuclease from Thermus aquaticus. Proc Natl Acad Sci U S A. 1977 Feb;74(2):542–546. doi: 10.1073/pnas.74.2.542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sealey P. G., Whittaker P. A., Southern E. M. Removal of repeated sequences from hybridisation probes. Nucleic Acids Res. 1985 Mar 25;13(6):1905–1922. doi: 10.1093/nar/13.6.1905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  34. Van Herle A. J., Vassart G., Dumont J. E. Control of thyroglobulin synthesis and secretion. (First of two parts). N Engl J Med. 1979 Aug 2;301(5):239–249. doi: 10.1056/NEJM197908023010504. [DOI] [PubMed] [Google Scholar]
  35. Wyman A. R., Wolfe L. B., Botstein D. Propagation of some human DNA sequences in bacteriophage lambda vectors requires mutant Escherichia coli hosts. Proc Natl Acad Sci U S A. 1985 May;82(9):2880–2884. doi: 10.1073/pnas.82.9.2880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. van Ommen G. J., Arnberg A. C., Baas F., Brocas H., Sterk A., Tegelaers W. H., Vassart G., de Vijlder J. J. The human thyroglobulin gene contains two 15-17 kb introns near its 3'-end. Nucleic Acids Res. 1983 Apr 25;11(8):2273–2285. doi: 10.1093/nar/11.8.2273. [DOI] [PMC free article] [PubMed] [Google Scholar]

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