Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 Sep;70(3):489–495. doi: 10.1172/JCI110640

Genetic analysis of familial isolated growth hormone deficiency type I.

J A Phillips 3rd, J S Parks, B L Hjelle, J E Herd, L P Plotnick, C J Migeon, P H Seeburg
PMCID: PMC370249  PMID: 6286724

Abstract

Nuclear DNA from individuals belonging to nine different families in which two sibs were affected with isolated growth hormone deficiency type I were studied by restriction endonuclease analysis. By using 32P-labeled human growth hormone or the homologous human chorionic somatomammotropin complementary DNA (cDNA) sequences as a probe, the growth hormone genes of affected individuals from all families yielded normal restriction patterns. Polymorphic restriction endonuclease sites (HincII and MspI), which are closely linked to the structural gene for growth hormone on chromosome 17, were used as markers in linkage analysis of DNA of family members. Of the nine affected sib pairs two were concordant, three were possibly concordant, and four were discordant for both linked markers. Since only concordant sib pairs would have inherited the same growth hormone alleles, further studies to identify mutations of the growth hormone genes should be limited to this subgroup. It is unlikely that the discordance observed in four of the sib pairs is due to recombination, because the polymorphic HincII site is only 116 base-pairs from the -26 codon of the growth hormone gene. Thus, in at least four of the nine families, the mutation responsible for isolated growth hormone deficiency is not within or near the structural gene for growth hormone on chromosome 17.

Full text

PDF
493

Images in this article

491Image
on p.491
491Image
on p.491
492Image
on p.492

Selected References

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

  1. DeNoto F. M., Moore D. D., Goodman H. M. Human growth hormone DNA sequence and mRNA structure: possible alternative splicing. Nucleic Acids Res. 1981 Aug 11;9(15):3719–3730. doi: 10.1093/nar/9.15.3719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Fiddes J. C., Seeburg P. H., DeNoto F. M., Hallewell R. A., Baxter J. D., Goodman H. M. Structure of genes for human growth hormone and chorionic somatomammotropin. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4294–4298. doi: 10.1073/pnas.76.9.4294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fleisher T. A., White R. M., Broder S., Nissley S. P., Blaese R. M., Mulvihill J. J., Olive G., Waldmann T. A. X-linked hypogammaglobulinemia and isolated growth hormone deficiency. N Engl J Med. 1980 Jun 26;302(26):1429–1434. doi: 10.1056/NEJM198006263022601. [DOI] [PubMed] [Google Scholar]
  4. George D. L., Phillips J. A., 3rd, Francke U., Seeburg P. H. The genes for growth hormone and chorionic somatomammotropin are on the long arm of human chromosome 17 in region q21 to qter. Hum Genet. 1981;57(2):138–141. doi: 10.1007/BF00282009. [DOI] [PubMed] [Google Scholar]
  5. Jeffreys A. J., Flavell R. A. A physical map of the DNA regions flanking the rabbit beta-globin gene. Cell. 1977 Oct;12(2):429–439. doi: 10.1016/0092-8674(77)90119-2. [DOI] [PubMed] [Google Scholar]
  6. Kowarski A. A., Schneider J., Ben-Galim E., Weldon V. V., Daughaday W. H. Growth failure with normal serum RIA-GH and low somatomedin activity: somatomedin restoration and growth acceleration after exogenous GH. J Clin Endocrinol Metab. 1978 Aug;47(2):461–464. doi: 10.1210/jcem-47-2-461. [DOI] [PubMed] [Google Scholar]
  7. Kunkel L. M., Smith K. D., Boyer S. H., Borgaonkar D. S., Wachtel S. S., Miller O. J., Breg W. R., Jones H. W., Jr, Rary J. M. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1245–1249. doi: 10.1073/pnas.74.3.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kurnit D. M., Hoehn H. Prenatal diagnosis of human genome variation. Annu Rev Genet. 1979;13:235–258. doi: 10.1146/annurev.ge.13.120179.001315. [DOI] [PubMed] [Google Scholar]
  9. Maniatis T., Fritsch E. F., Lauer J., Lawn R. M. The molecular genetics of human hemoglobins. Annu Rev Genet. 1980;14:145–178. doi: 10.1146/annurev.ge.14.120180.001045. [DOI] [PubMed] [Google Scholar]
  10. Maniatis T., Kee S. G., Efstratiadis A., Kafatos F. C. Amplification and characterization of a beta-globin gene synthesized in vitro. Cell. 1976 Jun;8(2):163–182. doi: 10.1016/0092-8674(76)90001-5. [DOI] [PubMed] [Google Scholar]
  11. Martial J. A., Hallewell R. A., Baxter J. D., Goodman H. M. Human growth hormone: complementary DNA cloning and expression in bacteria. Science. 1979 Aug 10;205(4406):602–607. doi: 10.1126/science.377496. [DOI] [PubMed] [Google Scholar]
  12. McDonell M. W., Simon M. N., Studier F. W. Analysis of restriction fragments of T7 DNA and determination of molecular weights by electrophoresis in neutral and alkaline gels. J Mol Biol. 1977 Feb 15;110(1):119–146. doi: 10.1016/s0022-2836(77)80102-2. [DOI] [PubMed] [Google Scholar]
  13. Niall H. D., Hogan M. L., Sauer R., Rosenblum I. Y., Greenwood F. C. Sequences of pituitary and placental lactogenic and growth hormones: evolution from a primordial peptide by gene reduplication. Proc Natl Acad Sci U S A. 1971 Apr;68(4):866–870. doi: 10.1073/pnas.68.4.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Orkin S. H., Kazazian H. H., Jr, Antonarakis S. E., Goff S. C., Boehm C. D., Sexton J. P., Waber P. G., Giardina P. J. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster. Nature. 1982 Apr 15;296(5858):627–631. doi: 10.1038/296627a0. [DOI] [PubMed] [Google Scholar]
  15. Owerbach D., Rutter W. J., Martial J. A., Baxter J. D., Shows T. B. Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans. Science. 1980 Jul 11;209(4453):289–292. doi: 10.1126/science.7384802. [DOI] [PubMed] [Google Scholar]
  16. Pavlakis G. N., Hizuka N., Gorden P., Seeburg P., Hamer D. H. Expression of two human growth hormone genes in monkey cells infected by simian virus 40 recombinants. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7398–7402. doi: 10.1073/pnas.78.12.7398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Phillips J. A., 3rd, Hjelle B. L., Seeburg P. H., Zachmann M. Molecular basis for familial isolated growth hormone deficiency. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6372–6375. doi: 10.1073/pnas.78.10.6372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rimoin D. L. Hereditary forms of growth hormone deficiency and resistance. Birth Defects Orig Artic Ser. 1976;12(6):15–29. [PubMed] [Google Scholar]
  19. Rimoin D. L., Schechter J. E. Histological and ultrastructural studies in isolated growth hormone deficiency. J Clin Endocrinol Metab. 1973 Nov;37(5):725–735. doi: 10.1210/jcem-37-5-725. [DOI] [PubMed] [Google Scholar]
  20. Shine J., Seeburg P. H., Martial J. A., Baxter J. D., Goodman H. M. Construction and analysis of recombinant DNA for human chorionic somatomammotropin. Nature. 1977 Dec 8;270(5637):494–499. doi: 10.1038/270494a0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Vogelstein B., Gillespie D. Preparative and analytical purification of DNA from agarose. Proc Natl Acad Sci U S A. 1979 Feb;76(2):615–619. doi: 10.1073/pnas.76.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES